Chinese Medical Sciences Journal ›› 2012, Vol. 27 ›› Issue (1): 18-23.doi: 10.1016/S1001-9294(12)60017-0

• Original Article • Previous Articles     Next Articles

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

Yi-jun Zhou*, Yu-ling Song, Hui Zhou, and Yan Li   

  1. Department of Endocrinology and Metabolism, Fourth Affiliated Hospital , China Medical University , Shenyang 110034, China
  • Received:2012-02-13 Revised:2012-04-01 Online:2012-03-30 Published:2012-03-30
  • About author:*Corresponding author Tel: 86-24-81006755, E-mail: zhoudoctor@ 163.com
  • Supported by:

    △ Supported by Grant from Department of Education of Liaoning Province (2008810).

Abstract: ObjectiveTo 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.

Key words: GPR40 /FFA1 , phospholipase C, antisense oligonucleotides , intracellular calcium, linoleic acid

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