ETA as a novel Kv2.1 inhibitor ameliorates β-cell dysfunction and hyperglycaemia

Clinical and Experimental Pharmacology & Physiology
Tingting ZhouJing Chen

Abstract

The Kv2.1 channel plays an important role in the regulation against pancreatic β-cell dysfunctions. Therefore, it is regarded as a promising target for drug discovery against type 2 diabetes. In the present study, we found that the small molecule 4-ethoxy-N-{[6-(2-thienyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl]methyl}aniline (ETA), a novel Kv2.1 inhibitor, may be capable of promoting glucose-stimulated insulin secretion and protecting from apoptosis in pancreatic INS-832/13 cells. The assay of ETA on type 2 diabetic mice induced by high-fat diet (HFD)/streptozocin (STZ) confirmed its potency in ameliorating glucose homeostasis. ETA administration reduced fasting blood glucose and glycated haemoglobin levels, improved oral glucose tolerance, and increased serum insulin levels in HFD/STZ mice. Mechanism study demonstrated that ETA protected INS-832/13 cells involving the regulation against protein kinase B and extracellular-regulated protein kinase 1/2 signalling pathways. Our study has confirmed the underlying regulation of Kv2.1 against β-cell function and also addressed the potential of ETA as a lead compound in the treatment of type 2 diabetes mellitus.

References

Jul 21, 2001·Molecular Endocrinology·P E MacDonaldM B Wheeler
Sep 25, 2002·The Journal of Biological Chemistry·Patrick E MacDonaldMichael B Wheeler
Jul 11, 2006·The Journal of Clinical Investigation·Marc Prentki, Christopher J Nolan
Sep 5, 2007·Cell Metabolism·David A JacobsonLouis H Philipson
Sep 2, 2010·Biochemical and Biophysical Research Communications·Shigeru YoshidaMasayuki Shibasaki
Nov 24, 2011·Experimental Diabetes Research·Zhongmin Alex MaJohn Turk
Nov 20, 2012·The Journal of Pharmacology and Experimental Therapeutics·Xiaoyan Nina LiYun-Ping Zhou
Jul 24, 2014·Expert Opinion on Drug Discovery·Xing XuXu Shen
Nov 21, 2014·Journal of Diabetes Investigation·Søs Skovsø
Apr 7, 2015·Biochemical and Biophysical Research Communications·Justyna JanikiewiczAgnieszka Dobrzyn
Apr 12, 2017·The Journal of Pharmacy and Pharmacology·Dahae LeeKi Sung Kang
Dec 9, 2017·Nature Reviews. Endocrinology·Yan ZhengFrank B Hu
Mar 13, 2018·The Journal of Steroid Biochemistry and Molecular Biology·Ying HuangChao Shen
Mar 29, 2018·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Chia-Liang LinYi-Hsien Hsieh

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Citations

Jan 1, 2021·Frontiers in Cell and Developmental Biology·Magdalena BachmannErich Gulbins

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