Autocrine insulin increases plasma membrane K-ATP channel via PI3K-VAMP2 pathway in MIN6 cells

作者：Xu Shanhua; Kim Ji Hee; Hwang Kyu Hee; Das Ranjan; Quan Xianglan; Tuyet Thi Nguyen; Kim Soo Jin; Cha Seung Kuy; Park Kyu Sang

来源：Biochemical and Biophysical Research Communications, 2015, 468(4): 752-757.

DOI：10.1016/j.bbrc.2015.11.028

• Insulin
• K-ATP channel
• Ca2+ signaling
• Phosphoinositide-3-kinase
• VAMP2
• MINE cells

Regulation of ATP-sensitive inwardly rectifying potassium (K-ATP) channel plays a critical role in metabolism-secretion coupling of pancreatic beta-cells. Released insulin from beta-cells inhibits insulin and glucagon secretion with autocrine and paracrine modes. However, molecular mechanism by which insulin inhibits hormone secretion remains elusive. Here, we investigated the effect of autocrine insulin on surface abundance of K-ATP channel in mouse clonal beta-cell line, MIN6. High glucose increased plasmalemmal sulfonylurea receptor 1 (SUR1), a component of K-ATP, channel as well as exogenous insulin treatment. SUR1 trafficking by high glucose or insulin was blocked by inhibition of phosphoinositide 3-kinase (PI3K) with wortmannin. Pretreatment with brefeldin A or silencing of vesicle-associated membrane protein 2 (VAMP2) abolished insulin-mediated upregulation of surface SUR1. Functionally, glucose-stimulated cytosolic Ca2+ ([Ca2+](i)) increase was blunted by insulin or diazoxide, a K-ATP channel opener. Insulin-induced suppression of [Ca2+](i) oscillation was prevented by an insulin receptor blacker. These results provide a novel molecular mechanism for autocrine negative feedback regulation of insulin secretion.

• 出版日期2015-12-25