Linoleic Acid Activates GPR40/FFA1 and Phospholipase C to Increase [Ca^(2+)]_i Release and Insulin Secretion in Islet Beta-Cells  

作　　者：Yi-jun Zhou Yu-ling Song Hui Zhou Yan Li 

机构地区：[1]Department of Endocrinology and Metabolism,Fourth Affiliated Hospital,China Medical University,Shenyang 110034,China

出　　处：《Chinese Medical Sciences Journal》2012年第1期18-23,共6页中国医学科学杂志（英文版）

基　　金：Supported by Grant from Department of Education of Liaoning Province (2008810)

摘　　要：Objective To elucidate GPR40/FFA1 and its downstream signaling pathways in regulating insulin secretion. Methods GPR40/FFA1 expression was detected by immunofluorescence imaging. We employed linoleic acid (LA), a free fatty acid that has a high affinity to the rat GPR40, and examined its effect on cytosolic free calcium concentration ([Ca2+]i) in primary rat β-cells by Fluo-3 intensity under confocal microscopy recording. Downregulation of GPR40/FFA1 expression by antisense oligonucleotides was performed in pancreatic β-cells, and insulin secretion was assessed by enzyme-linked immunosorbent assay. Results LA acutely stimulated insulin secretion from primary cultured rat pancreatic islets. LA induced significant increase of [Ca2+]i in the presence of 5.6 mmol/L and 11.1 mmol/L glucose, which was reflected by increased Fluo-3 intensity under confocal microscopy recording. LA-stimulated increase in [Ca2+]i and insulin secretion were blocked by inhibition of GPR40/FFA1 expression in β-cells after GPR40/FFA1-specific antisense treatment. In addition, the inhibition of phospholipase C (PLC) activity by U73122, PLC inhibitor, also markedly inhibited the LA-induced [Ca2+]i increase. Conclusion LA activates GPR40/FFA1 and PLC to stimulate Ca2+ release, resulting in an increase in [Ca2+]i and insulin secretion in rat islet β-cells.

关 键 词：GPR40 / FFA 1 phospholipase C antisense oligonucleotides intracellular calcium linoleic acid 

分 类 号：Q578[生物学—生物化学] S814.1[农业科学—畜牧学]