Possible involvement of normalized Pin1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice

Diabetology & Metabolic Syndrome
Masa-Ki InoueTomoichiro Asano

Abstract

Recently, clinical studies have shown the protective effects of sodium glucose co-transporter2 (SGLT2) inhibitors against progression of diabetic nephropathy, but the underlying molecular mechanisms remain unclear. Diabetic mice were prepared by injecting nicotinamide and streptozotocin, followed by high-sucrose diet feeding (NA/STZ/Suc mice). The SGLT2 inhibitor canagliflozin was administered as a 0.03% (w/w) mixture in the diet for 4 weeks. Then, various parameters and effects of canagliflozin on diabetic nephropathy were investigated. Canagliflozin administration to NA/STZ/Suc mice normalized hyperglycemia as well as elevated renal mRNA of collagen 1a1, 1a2, CTGF, TNFα and MCP-1. Microscopic observation revealed reduced fibrotic deposition in the kidneys of canagliflozin-treated NA/STZ/Suc mice. Interestingly, the protein level of Pin1, reportedly involved in the inflammation and fibrosis affecting several tissues, was markedly increased in the NA/STZ/Suc mouse kidney, but this was normalized with canagliflozin treatment. The cells showing increased Pin1 expression in the kidney were mainly mesangial cells, along with podocytes, based on immunohistochemical analysis. Furthermore, it was revealed that canagliflozin induced AM...Continue Reading

References

Apr 28, 2010·The Journal of Biological Chemistry·Zhenggang YangBing-Zhong Xue
May 23, 2012·The Journal of Biological Chemistry·Zhong-Jian ShenJames S Malter
Nov 1, 2012·The Journal of Biological Chemistry·Yusuke NakatsuTomoichiro Asano
Jun 23, 2015·Kidney International Supplements·Allan J CollinsShu-Cheng Chen
Feb 26, 2016·PloS One·Zhong-Jian ShenJames S Malter
Jun 15, 2016·The New England Journal of Medicine·Christoph WannerUNKNOWN EMPA-REG OUTCOME Investigators
Aug 20, 2016·Journal of the American Society of Nephrology : JASN·Hiddo J L HeerspinkVlado Perkovic
Sep 17, 2016·Biochemical and Biophysical Research Communications·Xue LiuYuxia Zhao
Jun 2, 2017·The Journal of Biological Chemistry·Yusuke NakatsuTomoichiro Asano
Jun 13, 2017·The New England Journal of Medicine·Bruce NealUNKNOWN CANVAS Program Collaborative Group
Aug 10, 2017·Current Hypertension Reports·Fan ZhangHongqing Zhang
Dec 13, 2018·American Journal of Physiology. Renal Physiology·Markus PirklbauerHerbert Schramek
Apr 17, 2019·The New England Journal of Medicine·Vlado PerkovicUNKNOWN CREDENCE Trial Investigators

❮ Previous
Next ❯

Citations

Jan 23, 2020·Clinical and Experimental Pharmacology & Physiology·Zahra Ashrafi JighehDavoud Sanajou
Jul 2, 2020·Diabetes, Metabolic Syndrome and Obesity : Targets and Therapy·Angelamellisy Revelian NdibalemaQiuling Fan
Dec 9, 2020·Cell Biology International·Xiao-Long ZhangZe-Hong Bai
Jan 29, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Shengfeng WanFengmin Shao
Jul 13, 2021·Diabetes, Obesity & Metabolism·Hongyan LiuDavid Z I Cherney
Aug 28, 2021·Antioxidants·Kai-Fan TsaiChien-Te Lee

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.