ID | 66886 |
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Kano, Yuzuki
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Yamaguchi, Satoshi
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Mise, Koki
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kawakita, Chieko
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Onishi, Yasuhiro
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Kurooka, Naoko
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Sugawara, Ryosuke
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Albuayjan, Haya Hamed Hassan
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Nakatsuka, Atsuko
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Eguchi, Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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Wada, Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
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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. |
Keywords | diabetes mellitus
diabetic nephropathy
metabolism
obesity
tubular epithelium
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Published Date | 2023-12-08
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Publication Title |
Kidney360
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Volume | volume5
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Issue | issue2
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Publisher | Ovid Technologies (Wolters Kluwer Health)
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Start Page | 182
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End Page | 194
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ISSN | 2641-7650
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Content Type |
Journal Article
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language |
English
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OAI-PMH Set |
岡山大学
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Copyright Holders | Copyright © 2023 The Author(s).
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File Version | publisher
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PubMed ID | |
DOI | |
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Related Url | isVersionOf https://doi.org/10.34067/kid.0000000000000333
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License | http://creativecommons.org/licenses/by-nc-nd/4.0/
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Citation | Kano, Yuzuki; Yamaguchi, Satoshi; Mise, Koki; Kawakita, Chieko; Onishi, Yasuhiro; Kurooka, Naoko; Sugawara, Ryosuke; Albuayjan, Haya Hamed Hassan; Nakatsuka, Atsuko; Eguchi, Jun; Wada, Jun. Inhibition of Amino Acids Influx into Proximal Tubular Cells Improves Lysosome Function in Diabetes. Kidney360 5(2):p 182-194, February 2024. | DOI: 10.34067/KID.0000000000000333
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Funder Name |
Japan Society for the Promotion of Science
Japan Agency for Medical Research and Development
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助成番号 | 22H03088
22ek0109445h0003
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