ID | 60130 |
フルテキストURL | |
著者 |
Fukushima, Kazuhiko
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kitamura, Shinji
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Kaken ID
publons
Tsuji, Kenji
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
researchmap
Sang, Yizhen
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Wada, Jun
Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
ORCID
Kaken ID
publons
researchmap
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抄録 | Obesity is supposed to cause renal injury via autophagy deficiency. Recently, sodium glucose co-transporter 2 inhibitors (SGLT2i) were reported to protect renal injury. However, the mechanisms of SGLT2i for renal protection are unclear. Here, we investigated the effect of SGLT2i for autophagy in renal proximal tubular cells (PTCs) on obesity mice. We fed C57BL/6J mice with a normal diet (ND) or high-fat and -sugar diet (HFSD) for nine weeks, then administered SGLT2i, empagliflozin, or control compound for one week. Each group contained N = 5. The urinary N-acetyl-beta-d-glucosaminidase level in the HFSD group significantly increased compared to ND group. The tubular damage was suppressed in the SGLT2i-HFSD group. In electron microscopic analysis, multi lamellar bodies that increased in autophagy deficiency were increased in PTCs in the HFSD group but significantly suppressed in the SGLT2i group. The autophagosomes of damaged mitochondria in PTCs in the HFSD group frequently appeared in the SGLT2i group. p62 accumulations in PTCs were significantly increased in HFSD group but significantly suppressed by SGLT2i. In addition, the mammalian target of rapamycin was activated in the HFSD group but significantly suppressed in SGLT2i group. These data suggest that SGLT2i has renal protective effects against obesity via improving autophagy flux impairment in PTCs on a HFSD.
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キーワード | sodium glucose co-transporter 2 inhibitor
mammalian target of rapamycin (mTOR)
autophagy
obesity
multi lamellar body
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発行日 | 2020-06-05
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出版物タイトル |
International Journal of Molecular Sciences
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巻 | 21巻
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号 | 11号
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出版者 | MDPI
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開始ページ | 4054
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ISSN | 1422-0067
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NCID | AA12038549
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2020 by the authors
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論文のバージョン | publisher
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PubMed ID | |
DOI | |
Web of Science KeyUT | |
関連URL | isVersionOf https://doi.org/10.3390/ijms21114054
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ライセンス | http://creativecommons.org/licenses/by/4.0/
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