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

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Regulation of ATP-sensitive inwardly rectifying potassium (KATP) channel plays a critical role in metabolism-secretion coupling of pancreatic β-cells. Released insulin from β-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 KATP channel in mouse clonal β-cell line, MIN6. High glucose increased plasmalemmal sulfonylurea receptor 1 (SUR1), a component of KATP 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 KATP channel opener. Insulin-induced suppression of [Ca2+]i oscillation was prevented by an insulin receptor blocker. These results provide a novel molecular mechanism for autocrine negative feedback regulation of insulin secretion.

Original languageEnglish
Pages (from-to)752-757
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume468
Issue number4
DOIs
Publication statusPublished - 2015 Dec 25

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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