Sodium Glucose Co-Transporter 2 Inhibitor Ameliorates Autophagic Flux Impairment on Renal Proximal Tubular Cells in Obesity Mice.

International Journal of Molecular Sciences
Kazuhiko FukushimaJun Wada

Abstract

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 g...Continue Reading

References

Apr 17, 2004·Kidney International·Kunitoshi IsekiShuichi Takishita
Feb 1, 2006·Clinical and Experimental Pharmacology & Physiology·Faruk OktemBumin Dündar
Oct 13, 2006·Journal of the American Society of Nephrology : JASN·Mauro AbbateGiuseppe Remuzzi
Aug 12, 2010·Methods in Molecular Biology·Isei Tanida, Satoshi Waguri
Jan 14, 2011·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Volker Vallon
May 14, 2011·Autophagy·Eeva-Liisa EskelinenPer O Seglen
Jun 7, 2016·Nature Reviews. Nephrology·Vivette D D'AgatiManuel Praga
Jun 15, 2016·The New England Journal of Medicine·Christoph WannerUNKNOWN EMPA-REG OUTCOME Investigators
Dec 10, 2016·Journal of the American Society of Nephrology : JASN·Takeshi YamamotoYoshitaka Isaka
Jun 9, 2017·Current Diabetes Reports·Munehiro KitadaDaisuke Koya
Sep 14, 2017·Npj Aging and Mechanisms of Disease·Taichi SugizakiYuichi Oike
Jan 21, 2018·Journal of Diabetes Investigation·Susumu TakagiDaisuke Koya
Mar 7, 2018·Scientific Reports·Michitsugu KamezakiKeiichi Tamagaki
Aug 4, 2018·The Journal of Pathology·Elena RampanelliJaklien C Leemans
Apr 29, 2020·International Journal of Molecular Sciences·Anton I KorbutVadim V Klimontov

❮ Previous
Next ❯

Citations

Sep 12, 2021·Nature Reviews. Endocrinology·Munehiro Kitada, Daisuke Koya

❮ Previous
Next ❯

Methods Mentioned

BETA
transmission electron microscopy
protein assay
electrophoresis

Software Mentioned

JMP
ImageJ

Related Concepts

Related Feeds

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagosome

An autophagosome is the formation of double-membrane vesicles that involve numerous proteins and cytoplasmic components. These double-membrane vesicles are then terminated at the lysosome where they are degraded. Discover the latest research on autophagosomes here.

Related Papers

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Giuseppe CiancioloGaetano La Manna
Journal of Nephrology
Antonio De PascalisGaetano La Manna
Current Pharmaceutical Design
Gerasimos SiasosDimitrios Tousoulis
International Journal of Molecular Sciences
Hidekatsu YanaiHisayuki Katsuyama
© 2022 Meta ULC. All rights reserved