Inhibition of glucose-stimulated insulin secretion by KCNJ15, a newly identified susceptibility gene for type 2 diabetes.

Diabetes
Koji OkamotoKatsushi Tokunaga

Abstract

Potassium inwardly rectifying channel, subfamily J, member 15 (KCNJ15) is a type 2 diabetes-associated risk gene, and Kcnj15 overexpression suppresses insulin secretion in rat insulinoma (INS1) cells. The aim of the current study was to characterize the role of Kcnj15 by knockdown of this gene in vitro and in vivo. Human islet cells were used to determine the expression of KCNJ15. Expression of KCNJ15 mRNA in islets was higher in subjects with type 2 diabetes. In INS1 cells, Kcnj15 expression was induced by high glucose-containing medium. Regulation of Kcnj15 by glucose and its effect on insulin secretion were analyzed in INS1 cells and in normal mice and diabetic mice by the inactivation of Kcnj15 using small interfering RNA. Knockdown of Kcnj15 increased the insulin secretion in vitro and in vivo. KCNJ15 and Ca(2+)-sensing receptor (CsR) interact in the kidney. Binding of Kcnj15 with CsR was also detected in INS1 cells. In conclusion, downregulation of Kcnj15 leads to increased insulin secretion in vitro and in vivo. The mechanism to regulate insulin secretion involves KCNJ15 and CsR.

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Citations

Jul 16, 2015·European Journal of Human Genetics : EJHG·Jinying ZhaoMomiao Xiong
Oct 15, 2013·Chemical Biology & Drug Design·Chuan TianTingguo Kang
May 20, 2015·The American Journal of Pathology·Koji OkamotoEisei Noiri
Dec 3, 2014·American Journal of Preventive Medicine·Yukako TatsumiKijyo Deura
Jun 23, 2012·Diabetes·Anne E W Mathews, Clayton E Mathews
Feb 13, 2018·Proceedings of the National Academy of Sciences of the United States of America·Xiaopu ZhouUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Nov 28, 2013·Pharmaceuticals·Olivia KoenigAndrea Nolte
Jul 4, 2013·Molecular Endocrinology·Eric M WausonMelanie H Cobb
Dec 30, 2014·Physiological Reviews·Francisco V SepúlvedaMaría Isabel Niemeyer

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Methods Mentioned

BETA
PCR
ELISA
immunoprecipitation
coimmunoprecipitation
electrophoresis
transfection

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