期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 263, 期 1-2, 页码 173-180出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2006.09.013
关键词
GPR40; free fatty acids; oleic acid; intracellular calcium; insulin secretion; pancreatic beta-cell; INS-1
Free fatty acids (FFA) cause a rise in cytosolic free Ca2+ ([Ca2+](i)) and stimulate insulin release from pancreatic beta-cells. The G-protein coupled receptor GPR40 can be activated by medium-and long-chain FFA. We investigated a potential role for GPR40 in the generation of the FFA-induced Ca2+ signal and insulin secretion. [Ca2+](i) was measured in primary mouse beta-cells and in INS-I cells, and insulin secretion was assessed from INS-I cells. GPR40 expression was determined by RT-PCR and downregulation of GPR40 expression by siRNA transfection was carried out in INS-I cells. A number of saturated, mono- and polyunsaturated medium- and long-chain FEN caused a rise in [Ca2+](i) both in primary mouse beta-cells and in INS-I cells. By contrast, the short-chain saturated caproic acid was ineffective at concentrations up to 300 mu M. In INS-I cells, the FFA-induced Ca2+ signal required mobilization of internal Ca2+ and Ca2+ influx through voltage-sensitive Ca2+ channels. RT-PCR analysis revealed that GPR40 is expressed in INS-1 cells. Downregulation of GPR40 by specific siRNA treatment lead to a significant inhibition of the FFA-induced [Ca2+](i) response and insulin secretion, indicating that the FFA-stimulated Ca2+ signal and insulin secretion involve activation of GPR40 in pancreatic beta-cells. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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