SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition.

• Material Type: 博士論文
• ISSN: 1932-7420
• Title: SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition.
• Volume: 32 3
• Author/Editor: 富田, 一聖; TOMITA, Issei
• Author Heading: 富田, 一聖; TOMITA, Issei
• Publication, Distribution, etc.: Elsevier B.V.
• Publication Date: 2020
• Publication Date (W3CDTF): 2020
• Periodical title: Cell metabolism
• Degree grantor/type: 滋賀医科大学
• Date Granted: 2021-03-09
• Date Granted (W3CDTF): 2021-03-09
• Dissertation Number: 甲第899号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第899号
• Text Language Code: eng
• Subject Heading: diabetic kidney disease; atherosclerosis; ketone body; SGLT2 inhibitor; lipolysis; ketolysis; mTORC1; nutrient-sensing signal; renal energy; metabolism
• Target Audience: 一般
• Note (General): pdf; SGLT2 inhibitors offer strong renoprotection in subjects with diabetic kidney disease (DKD). But the mechanism for such protection is not clear. Here, we report that in damaged proximal tubules of high-fat diet-fed ApoE-knockout mice, a model of non-proteinuric DKD, ATP production shifted from lipolysis to ketolysis dependent due to hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1). We further found that empagliflozin raised endogenous ketone body (KB) levels, and thus its use or treatment with 1,3-butanediol, a KB precursor, prevented decreases in renal ATP levels and organ damage in the mice. The renoprotective effect of empagliflozin was abolished by gene deletion of Hmgcs2, a rate-limiting enzyme of ketogenesis. Furthermore, KBs attenuated mTORC1-associated podocyte damage and proteinuria in diabetic db/db mice. Our findings show that SGLT2 inhibition-associated renoprotection is mediated by anelevation of KBs that in turn corrects mTORC1 hyperactivation that occurs in non-proteinuric and proteinuric DKD.; Thesis or Dissertation; 令和2年度; 10.1016/j.cmet.2020.06.020; 博士論文要旨
• DOI: info:doi/10.1016/j.cmet.2020.06.020; https://doi.org/info:doi/10.1016/j.cmet.2020.06.020
• Persistent ID (NDL): info:ndljp/pid/11710935; https://dl.ndl.go.jp/pid/11710935
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2021-08-09T17:15:52+09:00
• Date Created (W3CDTF): 2021-07-13
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Related Material (URI): http://hdl.handle.net/10422/00012998
• Periodical Title (URI): http://hdl.handle.net/10422/00013042; https://shiga-med.repo.nii.ac.jp/records/3944
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp

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2023-09-07 再収集