کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10749197 1050286 2015 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Autocrine insulin increases plasma membrane KATP channel via PI3K-VAMP2 pathway in MIN6 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Autocrine insulin increases plasma membrane KATP channel via PI3K-VAMP2 pathway in MIN6 cells
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 468, Issue 4, 25 December 2015, Pages 752-757
نویسندگان
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