start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=3
article-no=
start-page=e004237
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202405
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3)
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Introduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.
Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.
Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.
Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525.
en-copyright=
kn-copyright=
en-aut-name=UenoAsami
en-aut-sei=Ueno
en-aut-mei=Asami
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=OnishiYasuhiro
en-aut-sei=Onishi
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MiseKoki
en-aut-sei=Mise
en-aut-mei=Koki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=YamaguchiSatoshi
en-aut-sei=Yamaguchi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KannoAyaka
en-aut-sei=Kanno
en-aut-mei=Ayaka
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=NojimaIchiro
en-aut-sei=Nojima
en-aut-mei=Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=HiguchiChigusa
en-aut-sei=Higuchi
en-aut-mei=Chigusa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=UchidaHaruhito A.
en-aut-sei=Uchida
en-aut-mei=Haruhito A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=ShikataKenichi
en-aut-sei=Shikata
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MiyamotoSatoshi
en-aut-sei=Miyamoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=HidaKazuyuki
en-aut-sei=Hida
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=NakatoTatsuaki
en-aut-sei=Nakato
en-aut-mei=Tatsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=ToneAtsuhito
en-aut-sei=Tone
en-aut-mei=Atsuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=MatsuokaTakashi
en-aut-sei=Matsuoka
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=KameiShinji
en-aut-sei=Kamei
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=MurakamiKazutoshi
en-aut-sei=Murakami
en-aut-mei=Kazutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=ShimizuIkki
en-aut-sei=Shimizu
en-aut-mei=Ikki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
en-aut-name=MiyashitaKatsuhito
en-aut-sei=Miyashita
en-aut-mei=Katsuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=
en-aut-name=AndoShinichiro
en-aut-sei=Ando
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=
en-aut-name=NunoueTomokazu
en-aut-sei=Nunoue
en-aut-mei=Tomokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=26
ORCID=
affil-num=1
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center
kn-affil=
affil-num=14
en-affil=Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center
kn-affil=
affil-num=15
en-affil=Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center
kn-affil=
affil-num=16
en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital
kn-affil=
affil-num=17
en-affil=Department of Internal Medicine, Okayama Saiseikai General Hospital
kn-affil=
affil-num=18
en-affil=Okayama Saiseikai General Hospital
kn-affil=
affil-num=19
en-affil=Department of Diabetic Medicine, Kurashiki Central Hospital
kn-affil=
affil-num=20
en-affil=Department of Diabetic Medicine, Kurashiki Central Hospital
kn-affil=
affil-num=21
en-affil=Department of Diabetic Medicine, Kurashiki Central Hospital
kn-affil=
affil-num=22
en-affil=Sakakibara Heart Institute of Okayama
kn-affil=
affil-num=23
en-affil=Japanese Red Cross Okayama Hospital
kn-affil=
affil-num=24
en-affil=Okayama City General Medical Center
kn-affil=
affil-num=25
en-affil=Nunoue Clinic
kn-affil=
affil-num=26
en-affil=Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=78
cd-vols=
no-issue=2
article-no=
start-page=185
end-page=191
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=202404
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Reduced Immunogenicity of COVID-19 Vaccine in Obese Patients with Type 2 Diabetes: A Cross-Sectional Study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The global pandemic of coronavirus infection 2019 (COVID-19) was an unprecedented public health emergency. Several clinical studies reported that heart disease, lung disease, diabetes, hypertension, dyslipidemia, and obesity are critical risk factors for increased severity of and hospitalization for COVID-19. This is largely because patients with these underlying medical conditions can show poor immune responses to the COVID-19 vaccinations. Diabetes is one of the underlying conditions most highly associated with COVID-19 susceptibility and is considered a predictor of poor prognosis of COVID-19. We therefore investigated factors that influence the anti-SARS-CoV-2 spike IgG antibody titer after three doses of vaccination in patients with type 2 diabetes. We found that obesity was associated with low anti-SARS-CoV-2 spike IgG antibody titers following three-dose vaccination in type 2 diabetics. Obese patients with type 2 diabetes may have attenuated vaccine efficacy and require additional vaccination; continuous infection control should be considered in such patients.
en-copyright=
kn-copyright=
en-aut-name=TakahashiHiroko
en-aut-sei=Takahashi
en-aut-mei=Hiroko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NakayamaMasanori
en-aut-sei=Nakayama
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Office of Innovative Medicine, Organization for Research Strategy and Development, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=obesity
kn-keyword=obesity
en-keyword=type 2 diabetes
kn-keyword=type 2 diabetes
en-keyword=COVID-19
kn-keyword=COVID-19
en-keyword=vaccination
kn-keyword=vaccination
END
start-ver=1.4
cd-journal=joma
no-vol=5
cd-vols=
no-issue=2
article-no=
start-page=182
end-page=194
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20231208
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Inhibition of Amino Acids Influx into Proximal Tubular Cells Improves Lysosome Function in Diabetes
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background Inhibition of glucose influx into proximal tubular cells (PTCs) by sodium–glucose cotransporter 2 inhibitors revealed prominent therapeutic effects on diabetic kidney disease. Collectrin (CLTRN) serves as a chaperone for the trafficking of neutral amino acid (AA) transporters in the apical membranes of PTCs. We investigated the beneficial effects of reduced influx of AAs into PTCs in diabetes and obesity model of Cltrn−/y mice.
Methods Cltrn+/y and Cltrn−/y mice at age 5 weeks were assigned to standard diet and streptozotocin and high-fat diet (STZ-HFD)–treated groups.
Results At age 22–23 weeks, body weight and HbA1c levels significantly increased in STZ-HFD-Cltrn+/y compared with standard diet-Cltrn+/y; however, they were not altered in STZ-HFD-Cltrn−/y compared with STZ-HFD-Cltrn+/y. At age 20 weeks, urinary albumin creatinine ratio was significantly reduced in STZ-HFD-Cltrn−/y compared with STZ-HFD-Cltrn+/y. Under the treatments with STZ and HFD, the Cltrn gene deficiency caused significant increase in urinary concentration of AAs such as Gln, His, Gly, Thr, Tyr, Val, Trp, Phe, Ile, Leu, and Pro. In PTCs in STZ-HFD-Cltrn+/y, the enlarged lysosomes with diameter of 10 μm or more were associated with reduced autolysosomes, and the formation of giant lysosomes was prominently suppressed in STZ-HFD-Cltrn−/y. Phospho-mTOR and inactive form of phospho-transcription factor EB were reduced in STZ-HFD-Cltrn−/y compared with STZ-HFD-Cltrn+/y.
Conclusions The reduction of AAs influx into PTCs inactivated mTOR, activated transcription factor EB, improved lysosome function, and ameliorated vacuolar formation of PTCs in STZ-HFD-Cltrn−/y mice.
en-copyright=
kn-copyright=
en-aut-name=KanoYuzuki
en-aut-sei=Kano
en-aut-mei=Yuzuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=YamaguchiSatoshi
en-aut-sei=Yamaguchi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MiseKoki
en-aut-sei=Mise
en-aut-mei=Koki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KawakitaChieko
en-aut-sei=Kawakita
en-aut-mei=Chieko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=OnishiYasuhiro
en-aut-sei=Onishi
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KurookaNaoko
en-aut-sei=Kurooka
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=SugawaraRyosuke
en-aut-sei=Sugawara
en-aut-mei=Ryosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=AlbuayjanHaya Hamed Hassan
en-aut-sei=Albuayjan
en-aut-mei=Haya Hamed Hassan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=9
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=11
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=diabetes mellitus
kn-keyword=diabetes mellitus
en-keyword=diabetic nephropathy
kn-keyword=diabetic nephropathy
en-keyword=metabolism
kn-keyword=metabolism
en-keyword=obesity
kn-keyword=obesity
en-keyword=tubular epithelium
kn-keyword=tubular epithelium
END
start-ver=1.4
cd-journal=joma
no-vol=135
cd-vols=
no-issue=2
article-no=
start-page=81
end-page=84
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230801
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=Current findings on familial hypobetalipoproteinemia
kn-title=家族性低βリポタンパク血症に関する最近の知見
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=江口潤
kn-aut-sei=江口
kn-aut-mei=潤
aut-affil-num=1
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=和田淳
kn-aut-sei=和田
kn-aut-mei=淳
aut-affil-num=2
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学学術研究院医歯薬学域 腎・免疫・内分泌代謝内科学
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=岡山大学学術研究院医歯薬学域 腎・免疫・内分泌代謝内科学
en-keyword=低脂血症
kn-keyword=低脂血症
en-keyword=家族性低βリポタンパク血症
kn-keyword=家族性低βリポタンパク血症
en-keyword=無βリポタンパク血症
kn-keyword=無βリポタンパク血症
en-keyword=カイロミクロン停滞病
kn-keyword=カイロミクロン停滞病
END
start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=10
article-no=
start-page=1148
end-page=1156
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230713
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Role of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in hypertriglyceridemia and diabetes
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=In diabetes, the impairment of insulin secretion and insulin resistance contribute to hypertriglyceridemia, as the enzymatic activity of lipoprotein lipase (LPL) depends on insulin action. The transport of LPL to endothelial cells and its enzymatic activity are maintained by the formation of lipolytic complex depending on the multiple positive (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 [GPIHBP1], apolipoprotein C-II [APOC2], APOA5, heparan sulfate proteoglycan [HSPG], lipase maturation factor 1 [LFM1] and sel-1 suppressor of lin-12-like [SEL1L]) and negative regulators (APOC1, APOC3, angiopoietin-like proteins [ANGPTL]3, ANGPTL4 and ANGPTL8). Among the regulators, GPIHBP1 is a crucial molecule for the translocation of LPL from parenchymal cells to the luminal surface of capillary endothelial cells, and maintenance of lipolytic activity; that is, hydrolyzation of triglyceride into free fatty acids and monoglyceride, and conversion from chylomicron to chylomicron remnant in the exogenous pathway and from very low-density lipoprotein to low-density lipoprotein in the endogenous pathway. The null mutation of GPIHBP1 causes severe hypertriglyceridemia and pancreatitis, and GPIGBP1 autoantibody syndrome also causes severe hypertriglyceridemia and recurrent episodes of acute pancreatitis. In patients with type 2 diabetes, the elevated serum triglyceride levels negatively correlate with circulating LPL levels, and positively with circulating APOC1, APOC3, ANGPTL3, ANGPTL4 and ANGPTL8 levels. In contrast, circulating GPIHBP1 levels are not altered in type 2 diabetes patients with higher serum triglyceride levels, whereas they are elevated in type 2 diabetes patients with diabetic retinopathy and nephropathy. The circulating regulators of lipolytic complex might be new biomarkers for lipid and glucose metabolism, and diabetic vascular complications.
en-copyright=
kn-copyright=
en-aut-name=KurookaNaoko
en-aut-sei=Kurooka
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Dibaetes
kn-keyword=Dibaetes
en-keyword=GPIHBP1
kn-keyword=GPIHBP1
en-keyword=Lipoprotein lipase
kn-keyword=Lipoprotein lipase
END
start-ver=1.4
cd-journal=joma
no-vol=77
cd-vols=
no-issue=3
article-no=
start-page=243
end-page=254
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=202306
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Brown Adipose Tissue PPARγ Is Required for the Insulin-Sensitizing Action of Thiazolidinediones
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Brown adipose tissue (BAT) plays a critical role in metabolic homeostasis. BAT dysfunction is associated with the development of obesity through an imbalance between energy expenditure and energy intake. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulator of adipogenesis. However, the roles of PPARγ and thiazolidinediones (TZDs) in the regulation of BAT metabolism remain unclear. TZDs, which are selective PPARγ activators, improve systemic insulin resistance in animals and humans. In the present study, we generated brown adipocyte-specific PPARγ-deficient mice (BATγKO) to examine the in vivo roles of PPARγ and TZDs in BAT metabolism. In electron microscopic examinations, brown adipocyte-specific PPARγ deletion promoted severe whitening of brown fat and morphological alteration of mitochondria. Brown adipocyte-specific PPARγ deletion also reduced mRNA expression of BAT-selective genes. Although there was no difference in energy expenditure between control and BATγKO mice in calorimetry, norepinephrine-induced thermogenesis was impaired in BATγKO mice. Moreover, pioglitazone treatment improved diet-induced insulin resistance in the control mice but not in the BATγKO mice. These findings suggest that BAT PPARγ is necessary for the maintenance of brown adipocyte function and for the insulin-sensitizing action of TZDs.
en-copyright=
kn-copyright=
en-aut-name=ShibataYusuke
en-aut-sei=Shibata
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=PPARγ
kn-keyword=PPARγ
en-keyword=brown adipose tissue
kn-keyword=brown adipose tissue
en-keyword=thiazolidinediones
kn-keyword=thiazolidinediones
END
start-ver=1.4
cd-journal=joma
no-vol=76
cd-vols=
no-issue=3
article-no=
start-page=235
end-page=245
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=202206
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Roles of Transmembrane Protein 97 (TMEM97) in Adipose Tissue and Skeletal Muscle
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The combination of sarcopenia and obesity (sarcopenic obesity) is associated with the development of metabolic syndrome and cardiovascular events. The molecular pathways that develop sarcopenic obesity have studied intensively. Transmembrane protein 97 (TMEM97) is 176 amino acids conserved integral membrane protein with four transmembrane domains that is expressed in several types of cancer. Its physiological significance in adipose tissue and skeletal muscle has been unclear. We studied TMEM97-transgenic mice and mice lacking TMEM97, and our findings indicate that TMEM97 expression is regulated in adipose tissue and skeletal muscle from obesity. TMEM97 represses adipogenesis and promotes myogenesis in vitro. Fat-specific TMEM97 transgenic mice showed systemic insulin resistance. Mice overexpressing TMEM97 in skeletal muscle exhibited systemic insulin resistance. Mice lacking TMEM97 were protected against diet-induced obesity and insulin resistance. These phenotypes are associated with the effects of TMEM97 on inflammation genes in adipose tissue and skeletal muscle. Our findings indicates that there is a link between TMEM97 and chronic inflammation in obesity.
en-copyright=
kn-copyright=
en-aut-name=TentaMasafumi
en-aut-sei=Tenta
en-aut-mei=Masafumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology, and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=adipose tissue
kn-keyword=adipose tissue
en-keyword=skeletal muscle
kn-keyword=skeletal muscle
en-keyword=obesity
kn-keyword=obesity
END
start-ver=1.4
cd-journal=joma
no-vol=2022
cd-vols=
no-issue=
article-no=
start-page=3157841
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220110
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Objective. We examined whether or not day-to-day variations in lipid profiles, especially triglyceride (TG) variability, were associated with the exacerbation of diabetic kidney disease. Methods. We conducted a retrospective and observational study. First, 527 patients with type 2 diabetes mellitus (DM) who had had their estimated glomerular filtration rate (eGFR) checked every 6 months since 2012 for over 5 years were registered. Variability in postprandial TG was determined using the standard deviation (SD), SD adjusted (Adj-SD) for the number of measurements, and maximum minus minimum difference (MMD) during the first three years of follow-up. The endpoint was a & GE;40% decline from baseline in the eGFR, initiation of dialysis or death. Next, 181 patients who had no micro- or macroalbuminuria in February 2013 were selected from among the 527 patients for an analysis. The endpoint was the incidence of microalbuminuria, initiation of dialysis, or death. Results. Among the 527 participants, 110 reached a & GE;40% decline from baseline in the eGFR or death. The renal survival was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p=0.0073, 0.0059, and 0.0195, respectively). A lower SD, lower Adj-SD, and lower MMD were significantly associated with the renal survival in the adjusted model (hazard ratio, 1.62, 1.66, 1.59; 95% confidence intervals, 1.05-2.53, 1.08-2.58, 1.04-2.47, respectively). Next, among 181 participants, 108 developed microalbuminuria or death. The nonincidence of microalbuminuria was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p=0.0241, 0.0352, and 0.0474, respectively). Conclusions. Postprandial TG variability is a novel risk factor for eGFR decline and the incidence of microalbuminuria in patients with type 2 DM.
en-copyright=
kn-copyright=
en-aut-name=Matsuoka-UchiyamaNatsumi
en-aut-sei=Matsuoka-Uchiyama
en-aut-mei=Natsumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=UchidaHaruhito A.
en-aut-sei=Uchida
en-aut-mei=Haruhito A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=OkamotoShugo
en-aut-sei=Okamoto
en-aut-mei=Shugo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=OnishiYasuhiro
en-aut-sei=Onishi
en-aut-mei=Yasuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KatayamaKatsuyoshi
en-aut-sei=Katayama
en-aut-mei=Katsuyoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=Tsuchida-NishiwakiMariko
en-aut-sei=Tsuchida-Nishiwaki
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TakeuchiHidemi
en-aut-sei=Takeuchi
en-aut-mei=Hidemi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TakemotoRika
en-aut-sei=Takemoto
en-aut-mei=Rika
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=HadaYoshiko
en-aut-sei=Hada
en-aut-mei=Yoshiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=UmebayashiRyoko
en-aut-sei=Umebayashi
en-aut-mei=Ryoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=KurookaNaoko
en-aut-sei=Kurooka
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TsujiKenji
en-aut-sei=Tsuji
en-aut-mei=Kenji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=NakajimaHirofumi
en-aut-sei=Nakajima
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=ShikataKenichi
en-aut-sei=Shikata
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=13
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Nakashima Hospital
kn-affil=
affil-num=15
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=16
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=12
cd-vols=
no-issue=
article-no=
start-page=750261
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2022
dt-pub=20220103
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=MicroRNAs expressed in adipocytes are involved in transcriptional regulation of target mRNAs in obesity, but miRNAs critically involved in this process is not well characterized. Here, we identified upregulation of miR-221-3p and miR-222-3p in the white adipose tissues in C57BL/6 mice fed with high fat-high sucrose (HFHS) chow by RNA sequencing. Mir221 and Mir222 are paralogous genes and share the common seed sequence and Mir221/222AdipoKO mice fed with HFHS chow demonstrated resistance to the development of obesity compared with Mir221/222(flox/y). Ddit4 is a direct target of Mir221 and Mir222, and the upregulation of Ddit4 in Mir221/222AdipoKO was associated with the suppression of TSC2 (tuberous sclerosis complex 2)/mammalian target of rapamycin complex 1 (mTORC1)/S6K (ribosomal protein S6 kinase) pathway. The overexpression of miR-222-3p linked to enhanced adipogenesis, and it may be a potential candidate for miRNA-based therapy.
en-copyright=
kn-copyright=
en-aut-name=YamaguchiSatoshi
en-aut-sei=Yamaguchi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ZhangDongxiao
en-aut-sei=Zhang
en-aut-mei=Dongxiao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KurookaNaoko
en-aut-sei=Kurooka
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=SugawaraRyosuke
en-aut-sei=Sugawara
en-aut-mei=Ryosuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=AlbuayjanHaya Hamed Hassan
en-aut-sei=Albuayjan
en-aut-mei=Haya Hamed Hassan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=non-coding RNAs
kn-keyword=non-coding RNAs
en-keyword=microRNA
kn-keyword=microRNA
en-keyword=adipose tissues
kn-keyword=adipose tissues
en-keyword=Adipogenesis
kn-keyword=Adipogenesis
en-keyword=mTORC1
kn-keyword=mTORC1
END
start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=9
article-no=
start-page=e04574
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210907
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes mellitus: A report of two cases
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Immune checkpoint inhibitor-induced diabetes mellitus is a rare immune-related adverse event. This report illustrates clinical data and insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes.
en-copyright=
kn-copyright=
en-aut-name=FujiwaraNoriko
en-aut-sei=Fujiwara
en-aut-mei=Noriko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NodaYohei
en-aut-sei=Noda
en-aut-mei=Yohei
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KataokaHitomi
en-aut-sei=Kataoka
en-aut-mei=Hitomi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KagawaShunsuke
en-aut-sei=Kagawa
en-aut-mei=Shunsuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=2
en-affil=Department of Primary Care and Medical Education, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=3
en-affil=Diabetes Center, Okayama University Hospital
kn-affil=
affil-num=4
en-affil=Department of Otolaryngology-Head and Neck Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=6
en-affil=Department of Primary Care and Medical Education, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
affil-num=7
en-affil=Minimally Invasive Therapy Center, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine
kn-affil=
en-keyword=C-peptide
kn-keyword=C-peptide
en-keyword=diabetes mellitus
kn-keyword=diabetes mellitus
en-keyword=immune checkpoint inhibitor
kn-keyword=immune checkpoint inhibitor
en-keyword=insulin secretion
kn-keyword=insulin secretion
END
start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=
article-no=
start-page=668059
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210524
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2)
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear. Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease. Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24-2.55, P = 0.002) and Calsepa [High-Man (Man2-6)]: 1.56 (1.19-2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001-0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045-0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively]. Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE.
en-copyright=
kn-copyright=
en-aut-name=MiseKoki
en-aut-sei=Mise
en-aut-mei=Koki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ImamuraMariko
en-aut-sei=Imamura
en-aut-mei=Mariko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=YamaguchiSatoshi
en-aut-sei=Yamaguchi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HiguchiChigusa
en-aut-sei=Higuchi
en-aut-mei=Chigusa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MiyamotoSatoshi
en-aut-sei=Miyamoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=UchidaHaruhito A.
en-aut-sei=Uchida
en-aut-mei=Haruhito A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=HidaKazuyuki
en-aut-sei=Hida
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=NakatoTatsuaki
en-aut-sei=Nakato
en-aut-mei=Tatsuaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=ToneAtsuhito
en-aut-sei=Tone
en-aut-mei=Atsuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=MatsuokaTakashi
en-aut-sei=Matsuoka
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=KameiShinji
en-aut-sei=Kamei
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=MurakamiKazutoshi
en-aut-sei=Murakami
en-aut-mei=Kazutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=ShimizuIkki
en-aut-sei=Shimizu
en-aut-mei=Ikki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=MiyashitaKatsuhiro
en-aut-sei=Miyashita
en-aut-mei=Katsuhiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=AndoShinichiro
en-aut-sei=Ando
en-aut-mei=Shinichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
en-aut-name=NunoueTomokazu
en-aut-sei=Nunoue
en-aut-mei=Tomokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=21
ORCID=
en-aut-name=YoshidaMichihiro
en-aut-sei=Yoshida
en-aut-mei=Michihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=22
ORCID=
en-aut-name=YamadaMasao
en-aut-sei=Yamada
en-aut-mei=Masao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=23
ORCID=
en-aut-name=ShikataKenichi
en-aut-sei=Shikata
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=24
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=25
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Diabetes Center, Okayama University Hospital
kn-affil=
affil-num=7
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=9
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center
kn-affil=
affil-num=12
en-affil=Okayama Saiseikai General Hospital
kn-affil=
affil-num=13
en-affil=Okayama Saiseikai General Hospital
kn-affil=
affil-num=14
en-affil=Okayama Saiseikai General Hospital
kn-affil=
affil-num=15
en-affil=Kurashiki Central Hospital
kn-affil=
affil-num=16
en-affil=Kurashiki Central Hospital
kn-affil=
affil-num=17
en-affil=Kurashiki Central Hospital
kn-affil=
affil-num=18
en-affil=The Sakakibara Heart Institute of Okayama
kn-affil=
affil-num=19
en-affil=Japanese Red Cross Okayama Hospital
kn-affil=
affil-num=20
en-affil=Okayama City General Medical Center
kn-affil=
affil-num=21
en-affil=Nunoue Clinic
kn-affil=
affil-num=22
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=23
en-affil=GlycoTechnica Ltd.
kn-affil=
affil-num=24
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=25
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=cardiovascular event
kn-keyword=cardiovascular event
en-keyword=diabetes
kn-keyword=diabetes
en-keyword=lectins
kn-keyword=lectins
en-keyword=N-glycans
kn-keyword=N-glycans
en-keyword=urinary biomarkers
kn-keyword=urinary biomarkers
END
start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=1
article-no=
start-page=5991
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210316
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9(-/-) and Gal-9(wt/wt) C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9(-/-) mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9(wt/wt) mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9(-/-) mice receiving Gal-9(-/-) or Gal-9(wt/wt) bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9(wt/wt) mice receiving Gal-9(-/-) BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity.
en-copyright=
kn-copyright=
en-aut-name=NunoueTomokazu
en-aut-sei=Nunoue
en-aut-mei=Tomokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=YamaguchiSatoshi
en-aut-sei=Yamaguchi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NikiToshiro
en-aut-sei=Niki
en-aut-mei=Toshiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Immunology, Kagawa University
kn-affil=
affil-num=8
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=4
cd-vols=
no-issue=1
article-no=
start-page=373
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2021
dt-pub=20210319
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=A Vaspin-HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Proximal tubular cells (PTCs) are crucial for maintaining renal homeostasis, and tubular injuries contribute to progression of diabetic kidney disease (DKD). However, the roles of visceral adipose tissue-derived serine protease inhibitor (vaspin) in the development of DKD is not known. We found vaspin maintains PTCs through ameliorating ER stress, autophagy impairment, and lysosome dysfunction in DKD. Vaspin-/- obese mice showed enlarged and leaky lysosomes in PTCs associated with increased apoptosis, and these abnormalities were also observed in the patients with DKD. During internalization into PTCs, vaspin formed a complex with heat shock protein family A (Hsp70) member 1 like (HSPA1L) as well as 78kDa glucose-regulated protein (GRP78). Both vaspin-partners bind to clathrin heavy chain and involve in the endocytosis. Notably, albumin-overload enhanced extracellular release of HSPA1L and overexpression of HSPA1L dissolved organelle stresses, especially autophagy impairment. Thus, vapsin/HSPA1L-mediated pathways play critical roles in maintaining organellar function of PTCs in DKD.
en-copyright=
kn-copyright=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=YamaguchiSatoshi
en-aut-sei=Yamaguchi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KakutaShigeru
en-aut-sei=Kakuta
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=IwakuraYoichiro
en-aut-sei=Iwakura
en-aut-mei=Yoichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=SugiyamaHitoshi
en-aut-sei=Sugiyama
en-aut-mei=Hitoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=3
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, the University of Tokyo
kn-affil=
affil-num=5
en-affil=Research Institute for Biomedical Sciences, Tokyo University of Science
kn-affil=
affil-num=6
en-affil=Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
END
start-ver=1.4
cd-journal=joma
no-vol=10
cd-vols=
no-issue=1
article-no=
start-page=14928
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2020
dt-pub=20200910
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Dysfunction of CD8+PD-1+T cells in type 2 diabetes caused by the impairment of metabolism-immune axis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The metabolic changes and dysfunction in CD8+T cells may be involved in tumor progression and susceptibility to virus infection in type 2 diabetes (T2D). In C57BL/6JJcl mice fed with high fat-high sucrose chow (HFS), multifunctionality of CD8+splenic and tumor-infiltrating lymphocytes (TILs) was impaired and associated with enhanced tumor growth, which were inhibited by metformin. In CD8+splenic T cells from the HFS mice, glycolysis/basal respiration ratio was significantly reduced and reversed by metformin. In the patients with T2D (DM), multifunctionality of circulating CD8+PD-1+T cells stimulated with PMA/ionomycin as well as with HLA-A*24:02 CMV peptide was dampened, while metformin recovered multifunctionality. Both glycolysis and basal respiration were reduced in DM, and glycolysis was increased by metformin. The disturbance of the link between metabolism and immune function in CD8+PD-1+T cells in T2D was proved by recovery of antigen-specific and non-specific cytokine production via metformin-mediated increase in glycolytic activity.
en-copyright=
kn-copyright=
en-aut-name=NojimaIchiro
en-aut-sei=Nojima
en-aut-mei=Ichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=EikawaShingo
en-aut-sei=Eikawa
en-aut-mei=Shingo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=TomonobuNahoko
en-aut-sei=Tomonobu
en-aut-mei=Nahoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=HadaYoshiko
en-aut-sei=Hada
en-aut-mei=Yoshiko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=KajitaniNobuo
en-aut-sei=Kajitani
en-aut-mei=Nobuo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MiyamotoSatoshi
en-aut-sei=Miyamoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=ToneAtsuhito
en-aut-sei=Tone
en-aut-mei=Atsuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=UchidaHaruhito A.
en-aut-sei=Uchida
en-aut-mei=Haruhito A.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=ShikataKenichi
en-aut-sei=Shikata
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=UdonoHeiichiro
en-aut-sei=Udono
en-aut-mei=Heiichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=2
en-affil=Department of Hematology/Oncology, Hess Cancer Institute, Icahn School of Medicine At Mount Sinai
kn-affil=
affil-num=3
en-affil=Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=4
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=5
en-affil=Department of Internal Medicine, Diabetes Center, Okayama City Hospital
kn-affil=
affil-num=6
en-affil=Diabetes Center, Okayama S
kn-affil=italama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=7
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=8
en-affil=Diabetes Center, Okayama Saiseikai General Hospital
kn-affil=
affil-num=9
en-affil=Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=10
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=11
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=12
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=13
en-affil=Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=14
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
en-keyword=Cytokines
kn-keyword=Cytokines
en-keyword=Diabetes
kn-keyword=Diabetes
en-keyword=Endocrine system and metabolic diseases
kn-keyword=Endocrine system and metabolic diseases
en-keyword=Immunology
kn-keyword=Immunology
en-keyword=Tumour immunology
kn-keyword=Tumour immunology
END
start-ver=1.4
cd-journal=joma
no-vol=11
cd-vols=
no-issue=2
article-no=
start-page=97
end-page=104
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2019
dt-pub=20190916
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The hypoglycemia-prevention effect of sensor-augmented pump therapy with predictive low glucose management in Japanese patients with type 1 diabetes mellitus: a short-term study
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Aims/introduction
The predictive low glucose management (PLGM) system was introduced in March 2018 in Japan. Although there are some reports demonstrating the benefit of PLGM in preventing hypoglycemia, no data are currently available in Japanese patients with type 1 diabetes mellitus (T1DM). The aim of the present study is to evaluate the effect of PLGM with sensor-augmented pump therapy in the prevention of hypoglycemia in Japanese patients.
Materials and methods
We included 16 patients with T1DM who used the MiniMed®640G system after switching from the MiniMed®620G system. We retrospectively analysed the data of the continuous glucose monitoring system in 1 month after switching to MiniMed®640G.
Results
The area under the curve (AUC) of hypoglycemia of < 70 mg/dL was lowered from 0.42 ± 0.43 mg/dL day to 0.18 ± 0.18 mg/dL day (P = 0.012). Correspondingly, the duration of severe hypoglycemia (< 54 mg/dL) was reduced significantly from 15.3 ± 21.7 min/day to 4.8 ± 6.9 min/day (P = 0.019). The duration of hypoglycemia was reduced, but the reduction was not significant. Regarding the AUC for hyperglycemia > 180 mg/dL and the duration of hyperglycemia did not change. With the PLGM function, 79.3% of the predicted hypoglycemic events were avoided.
Conclusions
The hypoglycemia avoidance rate was comparable to those in previous reports. In addition, we demonstrated that PLGM can markedly suppress severe hypoglycemia without deteriorating glycemic control in Japanese T1DM patients. It is necessary to further investigate the effective use of the PLGM feature such as establishing a lower limit and the timing of resumption.
en-copyright=
kn-copyright=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=ToneAtsuhito
en-aut-sei=Tone
en-aut-mei=Atsuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=MiyamotoSatoshi
en-aut-sei=Miyamoto
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=ShikataKenichi
en-aut-sei=Shikata
en-aut-mei=Kenichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
affil-num=1
en-affil=Diabetes Center, Okayama University Hospital
kn-affil=
affil-num=2
en-affil=Diabetes Center, Okayama Saiseikai General Hospital
kn-affil=
affil-num=3
en-affil=Department of Primary Care and Medical Education, Okayama University
kn-affil=
affil-num=4
en-affil=Diabetes Center, Okayama Saiseikai General Hospital
kn-affil=
affil-num=5
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=6
en-affil=Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
kn-affil=
affil-num=7
en-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
kn-affil=
affil-num=8
en-affil=Center for Innovative Clinical Medicine, Okayama University Hospital
kn-affil=
affil-num=9
en-affil=Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Hypoglycemia
kn-keyword=Hypoglycemia
en-keyword=Predictive low glucose management (PLGM)
kn-keyword=Predictive low glucose management (PLGM)
en-keyword=Type 1 diabetes mellitus (T1DM)
kn-keyword=Type 1 diabetes mellitus (T1DM)
en-keyword=Sensor-augmented pump therapy (SAP)
kn-keyword=Sensor-augmented pump therapy (SAP)
END
start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=3
article-no=
start-page=e92647
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140525
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Pemt deficiency ameliorates endoplasmic reticulum stress in diabetic nephropathy
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Phosphatidylethanolamine N-methyltransferase (Pemt) catalyzes the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) mainly in the liver. Under an obese state, the upregulation of Pemt induces endoplasmic reticulum (ER) stress by increasing the PC/PE ratio in the liver. We targeted the Pemt gene in mice to explore the therapeutic impact of Pemt on the progression of diabetic nephropathy and diabetes, which was induced by the injection of streptozotocin (STZ). Although the blood glucose levels were similar in STZ-induced diabetic Pemt+/+ and Pemt−/−mice, the glomerular hypertrophy and albuminuria in Pemt−/− mice were significantly reduced. Pemt deficiency reduced the intraglomerular F4/80-positive macrophages, hydroethidine fluorescence, tubulointerstitial fibrosis and tubular atrophy. The expression of glucose-regulated protein-78 (GRP78) was enriched in the renal tubular cells in STZ-induced diabetic mice, and this was ameliorated by Pemt deficiency. In mProx24 renal proximal tubular cells, the treatment with ER-stress inducers, tunicamycin and thapsigargin, increased the expression of GRP78, which was reduced by transfection of a shRNA lentivirus for Pemt (shRNA-Pemt). The number of apoptotic cells in the renal tubules was significantly reduced in Pemt−/− diabetic mice, and shRNA-Pemt upregulated the phosphorylation of Akt and decreased the cleavage of caspase 3 and 7 in mProx24 cells. Taken together, these findings indicate that the inhibition of Pemt activity ameliorates the ER stress associated with diabetic nephropathy in a model of type 1 diabetes and corrects the functions of the three major pathways downstream of ER stress, i.e. oxidative stress, inflammation and apoptosis.
en-copyright=
kn-copyright=
en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=MurakamiKazutoshi
en-aut-sei=Murakami
en-aut-mei=Kazutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=InoueKentaro
en-aut-sei=Inoue
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TeramiTakahiro
en-aut-sei=Terami
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=HiguchiChigusa
en-aut-sei=Higuchi
en-aut-mei=Chigusa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=OgawaDaisuke
en-aut-sei=Ogawa
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=WatanabeEijiro
en-aut-sei=Watanabe
en-aut-mei=Eijiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
affil-num=1
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=2
en-affil=
kn-affil=Department of Diabetic Nephropathy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=3
en-affil=
kn-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=4
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=5
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=6
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=7
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=8
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=9
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=10
en-affil=
kn-affil=Department of Diabetic Nephropathy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=11
en-affil=
kn-affil=Dainippon Sumitomo Pharma
affil-num=12
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=13
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
END
start-ver=1.4
cd-journal=joma
no-vol=9
cd-vols=
no-issue=1
article-no=
start-page=e85594
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2014
dt-pub=20140122
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Nuclear Hormone Receptor Expression in Mouse Kidney and Renal Cell Lines
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Nuclear hormone receptors (NHRs) are transcription factors that regulate carbohydrate and lipid metabolism, immune responses, and inflammation. Although several NHRs, including peroxisome proliferator-activated receptor-γ (PPARγ) and PPARα, demonstrate a renoprotective effect in the context of diabetic nephropathy (DN), the expression and role of other NHRs in the kidney are still unrecognized. To investigate potential roles of NHRs in the biology of the kidney, we used quantitative real-time polymerase chain reaction to profile the expression of all 49 members of the mouse NHR superfamily in mouse kidney tissue (C57BL/6 and db/m), and cell lines of mesangial (MES13), podocyte (MPC), proximal tubular epithelial (mProx24) and collecting duct (mIMCD3) origins in both normal and high-glucose conditions. In C57BL/6 mouse kidney cells, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and COUP-TFIII were highly expressed. During hyperglycemia, the expression of the NHR 4A subgroup including neuron-derived clone 77 (Nur77), nuclear receptor-related factor 1, and neuron-derived orphan receptor 1 significantly increased in diabetic C57BL/6 and db/db mice. In renal cell lines, PPARδ was highly expressed in mesangial and proximal tubular epithelial cells, while COUP-TFs were highly expressed in podocytes, proximal tubular epithelial cells, and collecting duct cells. High-glucose conditions increased the expression of Nur77 in mesangial and collecting duct cells, and liver x receptor α in podocytes. These data demonstrate NHR expression in mouse kidney cells and cultured renal cell lines and suggest potential therapeutic targets in the kidney for the treatment of DN.
en-copyright=
kn-copyright=
en-aut-name=OgawaDaisuke
en-aut-sei=Ogawa
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TeramiNaoto
en-aut-sei=Terami
en-aut-mei=Naoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HatanakaTakashi
en-aut-sei=Hatanaka
en-aut-mei=Takashi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TachibanaHiromi
en-aut-sei=Tachibana
en-aut-mei=Hiromi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=Sato HoriguchiChikage
en-aut-sei=Sato Horiguchi
en-aut-mei=Chikage
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=NishiiNaoko
en-aut-sei=Nishii
en-aut-mei=Naoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=
kn-affil=Department of Diabetic Nephropathy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=2
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=3
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=4
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=5
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=6
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=7
en-affil=
kn-affil=Department of Diabetic Nephropathy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=8
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=9
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=10
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
END
start-ver=1.4
cd-journal=joma
no-vol=6
cd-vols=
no-issue=
article-no=
start-page=21721
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2016
dt-pub=20160217
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Insufficiency of phosphatidylethanolamine N-methyltransferase is risk for lean non-alcoholic steatohepatitis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract= Although obesity is undoubtedly major risk for non-alcoholic steatohepatitis (NASH), the presence of lean NASH patients with normal body mass index has been recognized. Here, we report that the insufficiency of phosphatidylethanolamine N-methyltransferase (PEMT) is a risk for the lean NASH. The Pemt−/− mice fed high fat-high sucrose (HFHS) diet were protected from diet-induced obesity and diabetes, while they demonstrated prominent steatohepatitis and developed multiple liver tumors. Pemt exerted inhibitory effects on p53-driven transcription by forming the complex with clathrin heavy chain and p53, and Pemt−/− mice fed HFHS diet demonstrated prominent apoptosis of hepatocytes. Furthermore, hypermethylation and suppressed mRNA expression of F-box protein 31 and hepatocyte nuclear factor 4α resulted in the prominent activation of cyclin D1. PEMT mRNA expression in liver tissues of NASH patients was significantly lower than those with simple steatosis and we postulated the distinct clinical entity of lean NASH with insufficiency of PEMT activities.
en-copyright=
kn-copyright=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=MatsuyamaMakoto
en-aut-sei=Matsuyama
en-aut-mei=Makoto
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=YamaguchiSatoshi
en-aut-sei=Yamaguchi
en-aut-mei=Satoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MurakamiKazutoshi
en-aut-sei=Murakami
en-aut-mei=Kazutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=OgawaDaisuke
en-aut-sei=Ogawa
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=WadaNozomu
en-aut-sei=Wada
en-aut-mei=Nozomu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=YasunakaTetsuya
en-aut-sei=Yasunaka
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=IkedaFusao
en-aut-sei=Ikeda
en-aut-mei=Fusao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TakakiAkinobu
en-aut-sei=Takaki
en-aut-mei=Akinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=WatanabeEijiro
en-aut-sei=Watanabe
en-aut-mei=Eijiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=2
en-affil=
kn-affil=Shigei Medical Research Institute
affil-num=3
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=4
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=5
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=6
en-affil=
kn-affil=Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=7
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=8
en-affil=
kn-affil=Department of Diabetic Nephropathy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=9
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=10
en-affil=
kn-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=11
en-affil=
kn-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=12
en-affil=
kn-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=13
en-affil=
kn-affil=Dainippon Sumitomo Pharma
affil-num=14
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
END
start-ver=1.4
cd-journal=joma
no-vol=5
cd-vols=
no-issue=
article-no=
start-page=16920
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=2015
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Beneficial impact of Gpnmb and its significance as a biomarker in nonalcoholic steatohepatitis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Gpnmb is classified as a type 1 membrane protein and its soluble form is secreted by ADAM10-mediated cleavage. Gpnmb mRNA was found in the Kupffer cells and white adipose tissues (WATs) and its upregulation in obesity was recently found. Here, we generated aP2 promoter-driven Gpnmb transgenic (Tg) mice and the overexpression of Gpnmb ameliorated the fat accumulation and fibrosis of the liver in diet-induced obesity model. Soluble form of Gpnmb in sera was elevated in Gpnmb Tg mice and Gpnmb concentrated in hepatic macrophages and stellate cells interacted with calnexin, which resulted in the reduction of oxidative stress. In the patients with non-alcoholic steatohepatitis, serum soluble GPNMB concentrations were higher compared with the patients with simple steatosis. The GPNMB is a promising biomarker and therapeutic target for the development and progression of NAFLD in obesity.
en-copyright=
kn-copyright=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=MurakamiKazutoshi
en-aut-sei=Murakami
en-aut-mei=Kazutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=KanzakiMotoko
en-aut-sei=Kanzaki
en-aut-mei=Motoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=NunoueTomokazu
en-aut-sei=Nunoue
en-aut-mei=Tomokazu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=HidaKazuyuki
en-aut-sei=Hida
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=WadaNozomu
en-aut-sei=Wada
en-aut-mei=Nozomu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=YasunakaTetsuya
en-aut-sei=Yasunaka
en-aut-mei=Tetsuya
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=IkedaFusao
en-aut-sei=Ikeda
en-aut-mei=Fusao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=TakakiAkinobu
en-aut-sei=Takaki
en-aut-mei=Akinobu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=YamamotoKazuhide
en-aut-sei=Yamamoto
en-aut-mei=Kazuhide
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=KiyonariHiroshi
en-aut-sei=Kiyonari
en-aut-mei=Hiroshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
affil-num=1
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=2
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=3
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=4
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=5
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=6
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=7
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=8
en-affil=
kn-affil=Department of Diabetes and Metabolism, National Hospital Organization Okayama Medical center
affil-num=9
en-affil=
kn-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=10
en-affil=
kn-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=11
en-affil=
kn-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=12
en-affil=
kn-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=13
en-affil=
kn-affil=Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=14
en-affil=
kn-affil=Animal Resource Development Unit
affil-num=15
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=16
en-affil=
kn-affil=Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
END
start-ver=1.4
cd-journal=joma
no-vol=6
cd-vols=
no-issue=
article-no=
start-page=233
end-page=240
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20131022
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Urinary angiotensinogen is a marker for tubular injuries in patients with type 2 diabetes
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Purpose: Urinary angiotensinogen has been reported as a marker for the activation of intrarenal renin–angiotensin system (RAS) in various kidney diseases. To investigate the importance of urinary angiotensinogen in diabetic nephropathy, we compared the urinary levels of angiotensinogen, albumin, and α1-microglobulin.
Materials and methods: Japanese patients with type 2 diabetes at various stages of nephropathy (n=85) were enrolled, and we measured albumin/creatinine ratio (ACR) and urinary excretion of angiotensinogen and α1-microglobulin. We also compared the clinical data of the patients treated with or without angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (RAS inhibitors [+], n=51; RAS inhibitors [−], n=34).
Results: Urinary angiotensinogen levels positively correlated with ACR (r =0.367, P=3.84×10-4) and urinary α1-microglobulin (r=0.734, P=1.32 × 10-15), while they negatively correlated with estimated glomerular filtration ratio (eGFR) (r=−0.350, P=1.02 × 10-3) and high-density lipoprotein cholesterol (r=−0.216, P=0.049). Multiple regression analysis was carried out to predict urinary angiotensinogen levels by employing eGFR, ACR, and urinary α1-microglobulin as independent variables; only urinary α1-microglobulin entered the regression equation at a significant level. Although ACR was higher in the RAS inhibitors (+) group, urinary α1-microglobulin and angiotensinogen did not show significant increase in the RAS inhibitors (+) group.
Conclusion: Urinary angiotensinogen is well correlated with urinary α1-microglobulin and reflected the tubular injuries which may be associated with the intrarenal RAS activation in patients with type 2 diabetes.
en-copyright=
kn-copyright=
en-aut-name=TeramiTakahiro
en-aut-sei=Terami
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=InoueKentaro
en-aut-sei=Inoue
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=OgawaDaisuke
en-aut-sei=Ogawa
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=MurakamiKazutoshi
en-aut-sei=Murakami
en-aut-mei=Kazutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
affil-num=1
en-affil=
kn-affil=Department of Medicine and Clinical Science,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=2
en-affil=
kn-affil=Department of Medicine and Clinical Science,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=3
en-affil=
kn-affil=Department of Medicine and Clinical Science,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=4
en-affil=
kn-affil=Department of Medicine and Clinical Science,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=5
en-affil=
kn-affil=Department of Medicine and Clinical Science,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=6
en-affil=
kn-affil=Department of Medicine and Clinical Science,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=7
en-affil=
kn-affil=Department of Medicine and Clinical Science,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=8
en-affil=
kn-affil=Department of Medicine and Clinical Science,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=9
en-affil=
kn-affil=Department of Medicine and Clinical Science,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
affil-num=10
en-affil=
kn-affil=Department of Medicine and Clinical Science,Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
en-keyword=diabetic nephropathy
kn-keyword=diabetic nephropathy
en-keyword=urinary biomarkers
kn-keyword=urinary biomarkers
en-keyword=renin–angiotensin system
kn-keyword=renin–angiotensin system
en-keyword=angiotensinogen
kn-keyword=angiotensinogen
en-keyword=α1-microglobulin
kn-keyword=α1-microglobulin
en-keyword=albumin
kn-keyword=albumin
END
start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=10
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20131015
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Urinary Fetuin-A Is a Novel Marker for Diabetic Nephropathy in Type 2 Diabetes Identified by Lectin Microarray
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=We analyzed the urine samples of patients with type 2 diabetes at various stages of diabetic nephropathy by lectin microarray to identify a biomarker to predict the progression of diabetic nephropathy. Japanese patients with type 2 diabetes at various stages of nephropathy were enrolled and we performed lectin microarray analyses (n = 17) and measured urinary excretion of fetuin-A (n = 85). The increased signals of urine samples were observed in Sia alpha 2-6Gal/GalNAc-binding lectins (SNA, SSA, TJA-I) during the progression of diabetic nephropathy. We next isolated sialylated glycoproteins by using SSA-lectin affinity chromatography and identified fetuin-A by liquid chromatography-tandem mass spectrometer. Urinary excretion of fetuin-A significantly increased during the progression of albuminuria (A1, 0.40 +/- 0.43; A2, 0.60 +/- 0.53; A3 1.57 +/- 1.13 ng/gCr; p = 7.29x10(-8)) and of GFR stages (G1, 0.39 +/- 0.39; G2, 0.49 +/- 0.45; G3, 1.25 +/- 1.18; G4, 1.34 +/- 0.80 ng/gCr; p = 3.89x10(-4)). Multivariate logistic regression analysis was employed to assess fetuin-A as a risk for diabetic nephropathy with microalbuminuria or GFR<60 mL/min. Fetuin-A is demonstrated as a risk factor for both microalbuminuria and reduction of GFR in diabetic nephropathy with the odds ratio of 4.721 (1.881-11.844) and 3.739 (1.785-7.841), respectively. Collectively, the glycan profiling analysis is useful method to identify the urine biomarkers and fetuin-A is a candidate to predict the progression of diabetic nephropathy.
en-copyright=
kn-copyright=
en-aut-name=InoueKentaro
en-aut-sei=Inoue
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MurakamiKazutoshi
en-aut-sei=Murakami
en-aut-mei=Kazutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=OgawaDaisuke
en-aut-sei=Ogawa
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TeramiTakahiro
en-aut-sei=Terami
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=ToneAtsuhito
en-aut-sei=Tone
en-aut-mei=Atsuhito
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=IsedaIzumi
en-aut-sei=Iseda
en-aut-mei=Izumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=HidaKazuyuki
en-aut-sei=Hida
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=YamadaMasao
en-aut-sei=Yamada
en-aut-mei=Masao
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=OgawaTomohisa
en-aut-sei=Ogawa
en-aut-mei=Tomohisa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=10
en-affil=
kn-affil=Natl Hosp Org, Okayama Med Ctr, Dept Diabet & Metab
affil-num=11
en-affil=
kn-affil=Natl Hosp Org, Okayama Med Ctr, Dept Diabet & Metab
affil-num=12
en-affil=
kn-affil=Natl Hosp Org, Okayama Med Ctr, Dept Diabet & Metab
affil-num=13
en-affil=
kn-affil=GlycoTechnica Ltd
affil-num=14
en-affil=
kn-affil=GP BioSci Co Ltd
affil-num=15
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
END
start-ver=1.4
cd-journal=joma
no-vol=14
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20130122
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Galectin-9 (Gal-9) induces apoptosis in activated T helper 1 (T(H)1) cells as a ligand for T cell immunoglobulin mucin-3 (Tim-3). Gal-9 also inhibits the G1 phase cell cycle arrest and hypertrophy in db/db mice, the hallmark of early diabetic nephropathy, by reversing the high glucose-induced up-regulation of cyclin dependent kinase inhibitors such as p27(Kip1) and p21(Cip1).
Methods: We investigated the serum levels of Gal-9 in the patients with type 2 diabetes and various stages of chronic kidney disease (CKD) (n = 182).
Results: Serum Gal-9 levels in the patients with type 2 diabetes were 131.9 +/- 105.4 pg/ml and Log(10)Gal-9 levels significantly and positively correlated with age (r = 0.227, p = 0.002), creatinine (r = 0.175, p = 0.018), urea nitrogen (r = 0.162, p = 0.028) and osmotic pressure (r = 0.187, p = 0.014) and negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.188, p = 0.011). Log(10)Gal-9 levels increased along with the progression of GFR categories of G1 to G4, and they were statistically significant by Jonckheere-Terpstra test (p = 0.012). Log(10)Gal-9 levels remained similar levels in albuminuria stages of A1 to A3.
Conclusion: The elevation of serum Gal-9 in the patients with type 2 diabetes is closely linked to GFR and they may be related to the alteration of the immune response and inflammation of the patients with type 2 diabetes and CKD.
en-copyright=
kn-copyright=
en-aut-name=KuroseYuko
en-aut-sei=Kurose
en-aut-mei=Yuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=KanzakiMotoko
en-aut-sei=Kanzaki
en-aut-mei=Motoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MurakamiKazutoshi
en-aut-sei=Murakami
en-aut-mei=Kazutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=InoueKentaro
en-aut-sei=Inoue
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=TeramiTakahiro
en-aut-sei=Terami
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=WatanabeMayu
en-aut-sei=Watanabe
en-aut-mei=Mayu
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=HiguchiChigusa
en-aut-sei=Higuchi
en-aut-mei=Chigusa
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=MiyatakeNobuyuki
en-aut-sei=Miyatake
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=3
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=4
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=5
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=6
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=7
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=8
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=9
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=10
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=11
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=12
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=13
en-affil=
kn-affil=Kagawa Univ, Fac Med, Dept Hyg
affil-num=14
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
en-keyword=Type 2 diabetes
kn-keyword=Type 2 diabetes
en-keyword=Glomerular filtration
kn-keyword=Glomerular filtration
en-keyword=Inflammation
kn-keyword=Inflammation
en-keyword=Kidney disease
kn-keyword=Kidney disease
en-keyword=Nephropathy
kn-keyword=Nephropathy
END
start-ver=1.4
cd-journal=joma
no-vol=61
cd-vols=
no-issue=11
article-no=
start-page=2823
end-page=2832
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201211
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=It is unknown whether adipokines derived from adipose tissues modulate endoplasmic reticulum (ER) stress induced in obesity. Here, we show that visceral adipose tissue-derived serine protease inhibitor (vaspin) binds to cell-surface 78-kDa glucose-regulated protein (GRP78), which is recruited from ER to plasma membrane under ER stress. Vaspin transgenic mice were protected from diet-induced obesity, glucose intolerance, and hepatic steatosis, while vaspin-deficient mice developed glucose intolerance associated with upregulation of ER stress markers. With tandem affinity tag purification using HepG2 cells, we identified GRP78 as an interacting molecule. The complex formation of vaspin, GRP78, and murine tumor cell DnaJ-like protein 1 (MTJ-1) (DnaJ homolog, subfamily C, member 1) on plasma membrane was confirmed by cell-surface labeling with biotin and immunoprecipitation in liver tissues and H-4-II-E-C3 cells. The addition of recombinant human vaspin in the cultured H-4-II-E-C3 cells also increased the phosphorylation of Akt and AMP-activated protein kinase (AMPK) in a dose-dependent manner, and anti-GRP78 antibodies completely abrogated the vaspin-induced upregulation of pAkt and pAMPK Vaspin is a novel ligand for cell-surface GRP78/MTJ-1 complex, and its subsequent signals exert beneficial effects on ER stress-induced metabolic dysfunctions. Diabetes 61:2823-2832, 2012
en-copyright=
kn-copyright=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=IsedaIzumi
en-aut-sei=Iseda
en-aut-mei=Izumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=HigashioKanji
en-aut-sei=Higashio
en-aut-mei=Kanji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MurakamiKazutoshi
en-aut-sei=Murakami
en-aut-mei=Kazutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KanzakiMotoko
en-aut-sei=Kanzaki
en-aut-mei=Motoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=InoueKentaro
en-aut-sei=Inoue
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=TeramiTakahiro
en-aut-sei=Terami
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=HidaKazuyuki
en-aut-sei=Hida
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=HoriguchiChikage Sato
en-aut-sei=Horiguchi
en-aut-mei=Chikage Sato
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=OgawaDaisuke
en-aut-sei=Ogawa
en-aut-mei=Daisuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=MatsukiYasushi
en-aut-sei=Matsuki
en-aut-mei=Yasushi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=HiramatsuRyuji
en-aut-sei=Hiramatsu
en-aut-mei=Ryuji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
en-aut-name=YagitaHideo
en-aut-sei=Yagita
en-aut-mei=Hideo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=17
ORCID=
en-aut-name=KakutaShigeru
en-aut-sei=Kakuta
en-aut-mei=Shigeru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=18
ORCID=
en-aut-name=IwakuraYoichiro
en-aut-sei=Iwakura
en-aut-mei=Yoichiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=19
ORCID=
en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=20
ORCID=
affil-num=1
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=2
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=3
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=4
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=5
en-affil=
kn-affil=Metabolome Pharmaceut Inc
affil-num=6
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=7
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=8
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=9
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=10
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=11
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci, Okayama
affil-num=12
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
affil-num=13
en-affil=
kn-affil=Okayama Univ, Dept Diabet Nephropathy, Grad Sch Med Dent & Pharmaceut Sci
affil-num=14
en-affil=
kn-affil=Okayama Univ, Dept Diabet Nephropathy, Grad Sch Med Dent & Pharmaceut Sci
affil-num=15
en-affil=
kn-affil=Dainippon Sumitomo Pharma, Genom Sci Labs
affil-num=16
en-affil=
kn-affil=Dainippon Sumitomo Pharma, Genom Sci Labs
affil-num=17
en-affil=
kn-affil=Juntendo Univ, Sch Med, Dept Immunol
affil-num=18
en-affil=
kn-affil=Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol
affil-num=19
en-affil=
kn-affil=Univ Tokyo, Inst Med Sci, Ctr Expt Med & Syst Biol
affil-num=20
en-affil=
kn-affil=Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci
END
start-ver=1.4
cd-journal=joma
no-vol=97
cd-vols=
no-issue=7
article-no=
start-page=E1202
end-page=E1207
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2012
dt-pub=201207
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Serum Vaspin Concentrations Are Closely Related to Insulin Resistance, and rs77060950 at SERPINA12 Genetically Defines Distinct Group with Higher Serum Levels in Japanese Population
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Context: Vaspin is an adipokine with insulin-sensitizing effects identified from visceral adipose tissues of genetically obese rats.
Objective: We investigated genetic and nongenetic factors that define serum concentrations of vaspin.
Design, Setting and Participants: Vaspin levels were measured with RIA in Japanese subjects with normal fasting plasma glucose (NFG; n = 259) and type 2 diabetes patients (T2D; n = 275). Single nucleotide polymorphisms (SNP) at SERPINA12 (vaspin) gene locus were discovered, and five SNP were genotyped in the subjects with varied body mass index (n = 1138).
Results: The level of serum vaspin in 93% of the samples was found to vary from 0.2 to nearly 2 ng/ml in NFG subjects (n = 259) and from 0.2 to nearly 3 ng/ml in T2D patients (n = 275) (Vaspin(Low) group), whereas a significant subpopulation (7%) in both groups displayed much higher levels of 10-40 ng/ml (Vaspin(High) group). In the Vaspin(Low) group, serum vaspin levels in T2D were significantly higher than healthy subjects (0.99 +/- 0.04 vs. 0.86 +/- 0.02 ng/ml; P < 0.01). Both in T2D and genotyped Japanese population, serum vaspin levels closely correlated with homeostasis model of assessment for insulin resistance rather than anthropometric parameters. By genotyping, rs77060950 tightly linked to serum vaspin levels, i.e. CC (0.6 +/- 0.4 ng/ml), CA (18.4 +/- 9.6 ng/ml), and AA (30.5 +/- 5.1 ng/ml) (P < 2 x 10(-16)). Putative GATA-2 and GATA-3 binding consensus site was found at rs77060950.
Conclusions: Serum vaspin levels were related to insulin resistance, and higher levels of serum vaspin in 7% of the Japanese population are closely linked to minor allele sequence (A) of rs77060950. (J Clin Endocrinol Metab 97: E1202-E1207, 2012)
en-copyright=
kn-copyright=
en-aut-name=TeshigawaraSanae
en-aut-sei=Teshigawara
en-aut-mei=Sanae
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=
en-aut-name=WadaJun
en-aut-sei=Wada
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=
en-aut-name=HidaKazuyuki
en-aut-sei=Hida
en-aut-mei=Kazuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=
en-aut-name=NakatsukaAtsuko
en-aut-sei=Nakatsuka
en-aut-mei=Atsuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=
en-aut-name=EguchiJun
en-aut-sei=Eguchi
en-aut-mei=Jun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=
en-aut-name=MurakamiKazutoshi
en-aut-sei=Murakami
en-aut-mei=Kazutoshi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=
en-aut-name=KanzakiMotoko
en-aut-sei=Kanzaki
en-aut-mei=Motoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=
en-aut-name=InoueKentaro
en-aut-sei=Inoue
en-aut-mei=Kentaro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=
en-aut-name=TeramiTakahiro
en-aut-sei=Terami
en-aut-mei=Takahiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=
en-aut-name=KatayamaAkihiro
en-aut-sei=Katayama
en-aut-mei=Akihiro
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=
en-aut-name=IsedaIzumi
en-aut-sei=Iseda
en-aut-mei=Izumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=11
ORCID=
en-aut-name=MatsushitaYuichi
en-aut-sei=Matsushita
en-aut-mei=Yuichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=12
ORCID=
en-aut-name=MiyatakeNobuyuki
en-aut-sei=Miyatake
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=13
ORCID=
en-aut-name=McDonaldJohn F.
en-aut-sei=McDonald
en-aut-mei=John F.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=14
ORCID=
en-aut-name=HottaKikuko
en-aut-sei=Hotta
en-aut-mei=Kikuko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=15
ORCID=
en-aut-name=MakinoHirofumi
en-aut-sei=Makino
en-aut-mei=Hirofumi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=16
ORCID=
affil-num=1
en-affil=
kn-affil=
affil-num=2
en-affil=
kn-affil=Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Med & Clin Sci
affil-num=3
en-affil=
kn-affil=
affil-num=4
en-affil=
kn-affil=
affil-num=5
en-affil=
kn-affil=
affil-num=6
en-affil=
kn-affil=
affil-num=7
en-affil=
kn-affil=Kagawa Univ, Fac Med, Dept Hyg
affil-num=8
en-affil=
kn-affil=
affil-num=9
en-affil=
kn-affil=
affil-num=10
en-affil=
kn-affil=
affil-num=11
en-affil=
kn-affil=
affil-num=12
en-affil=
kn-affil=
affil-num=13
en-affil=
kn-affil=Kagawa Univ, Fac Med, Dept Hyg
affil-num=14
en-affil=
kn-affil=Millipore Corp, Linco Res, St Charles
affil-num=15
en-affil=
kn-affil=Kyoto Univ, Grad Sch Med, Evidenced Based Med Res Ctr
affil-num=16
en-affil=
kn-affil=
END