Sodium-glucose cotransporter 2 inhibition normalizes glucose metabolism and suppresses oxidative stress in the kidneys of diabetic mice

Kidney International
Shinji TanakaTetsuhiro Tanaka

Abstract

It is unclear whether long-term sodium-glucose cotransporter 2 (SGLT2) inhibition such as that during the treatment of diabetes has deleterious effects on the kidney. Therefore, we first sought to determine whether abnormal glucose metabolism occurs in the kidneys of 22-week-old BTBR ob/ob diabetic mice. Second, the cumulative effect of chronic SGLT2 inhibition by ipragliflozin and 30% calorie restriction, either of which lowered blood glucose to a similar extent, on renal glucose metabolism was evaluated. Mass spectrometry-based metabolomics demonstrated that these diabetic mice exhibited an abnormal elevation in the renal pools of tricarboxylic acid cycle metabolites. This was almost completely nullified by SGLT2 inhibition and calorie restriction. Moreover, imaging mass spectrometry indicated an increased level of the tricarboxylic acid cycle intermediate, citrate, in the cortex of the diabetic mice. SGLT2 inhibition as well as calorie restriction almost completely eliminated citrate accumulation in the cortex. Furthermore, imaging mass spectrometry revealed that the accumulation of oxidized glutathione in the cortex of the kidneys, prominent in the glomeruli, was also canceled by SGLT2 inhibition and calorie restriction. Ef...Continue Reading

Citations

Apr 19, 2019·Diabetes/metabolism Research and Reviews·Federica BaruttaGabriella Gruden
Nov 15, 2019·Current Opinion in Nephrology and Hypertension·Naoki KashiharaEiichiro Kanda
Oct 9, 2019·Current Opinion in Nephrology and Hypertension·Marie ItoMasaomi Nangaku
Feb 6, 2020·Journal of Clinical Medicine·Teresa Caro-OrdieresJesús Egido
Dec 13, 2019·Journal of Diabetes Research·Yuyang WangPing Li
Jul 14, 2020·Journal of Diabetes Research·Jiarong LvShizhong Bu
Apr 16, 2020·International Journal of Molecular Sciences·Lucas Opazo-RíosJesús Egido
Jan 31, 2020·Journal of the American Society of Nephrology : JASN·Mai SugaharaMasaomi Nangaku
Aug 11, 2020·Oxidative Medicine and Cellular Longevity·Jing GuoWei Jing Liu
Sep 29, 2019·Kidney Research and Clinical Practice·Tomoko HondaMasaomi Nangaku
Oct 3, 2020·Nature Reviews. Nephrology·Adriana MartonJens Titze
Feb 27, 2020·Biomedicines·Keiichiro MatobaRimei Nishimura
Oct 18, 2020·Kidney International·Masaomi Nangaku
Dec 12, 2020·Kidney International·Amanda J Clark, Samir M Parikh
Jan 30, 2021·Diabetes & Metabolism Journal·Tomotaka YamazakiMasaomi Nangaku
Mar 2, 2021·Journal of Nephrology·Noriaki KuritaUNKNOWN Diabetes Distress and Care Registry at Tenri Study Group
Jan 14, 2020·Pharmacology & Therapeutics·Eiji SugiyamaYuki Sugiura
Jun 2, 2021·Nutrition, Metabolism, and Cardiovascular Diseases : NMCD·Amir RoointanAlieh Gholaminejad
Jul 29, 2021·Advanced Science·Sevgican DemirBilgen Ekim Üstünel
Aug 8, 2021·International Journal of Molecular Sciences·Anqi ZhangAkira Nishiyama
Aug 8, 2021·Drugs·Lucia Del VecchioSimonetta Genovesi
Aug 28, 2021·Antioxidants·Kai-Fan TsaiChien-Te Lee
Jul 17, 2021·Annual Review of Nutrition·Melissa InigoShawn C Burgess
Dec 18, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qingqing KeYang Zhou

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