title: Autocrine insulin increases plasma membrane K(ATP) channel via PI3K-VAMP2 pathway in MIN6 cells.
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 Ca(2+) ([Ca(2+)]i) increase was blunted by insulin or diazoxide, a KATP channel opener. Insulin-induced suppression of [Ca(2+)]i oscillation was prevented by an insulin receptor blocker. These results provide a novel molecular mechanism for autocrine negative feedback regulation of insulin secretion.
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea; Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Shanhua
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Ji-Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea; Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Kyu-Hee
authors.initials: KH
authors.lastname: Hwang
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Ranjan
authors.initials: R
authors.lastname: Das
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Xianglan
authors.initials: X
authors.lastname: Quan
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Tuyet Thi
authors.initials: TT
authors.lastname: Nguyen
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea; Department of Global Medical Science, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. Electronic address: skcha@yonsei.ac.kr.
authors.forename: Seung-Kuy
authors.initials: SK
authors.lastname: Cha
authors.affiliation: Department of Physiology, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. Electronic address: qsang@yonsei.ac.kr.
authors.forename: Kyu-Sang
authors.initials: KS
authors.lastname: Park
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D054086:KATP Channels; D051379:Mice; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism*
chemical_list: D007328:Insulin; D054086:KATP Channels; D050988:Vesicle-Associated Membrane Protein 2; C494808:vesicle-associated membrane protein 2, mouse; D058539:Phosphatidylinositol 3-Kinase; D011188:Potassium; D002118:Calcium
keywords: Ca(2+) signaling; Insulin; K(ATP) channel; MIN6 cells; Phosphoinositide-3-kinase; VAMP2