Linoleic Acid Activates GPR40/FFA1 and Phospholipase C to Increase [Ca²⁺]_i Release and Insulin Secretion in Islet Beta-Cells

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• 作者：Yi-jun Zhou ; ^{zhoudoctor@163.com} ; Yu-ling Song ; Hui Zhou ; Yan Li
• 关键词：GPR40/FFA1 ; phospholipase C ; antisense oligonucleotides ; intracellular calcium ; linoleic acid
• 刊名：Chinese Medical Sciences Journal
• 出版年：2012
• 期刊代码：P74_10019294
• 类别：med
• 出版时间：March, 2012
• 卷：27
• 期：1
• 页码：18-23
• 文件大小：307 K

摘要

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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 尾-cells by Fluo-3 intensity under confocal microscopy recording. Downregulation of GPR40/FFA1 expression by antisense oligonucleotides was performed in pancreatic 尾-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 尾-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 尾-cells.