Linoleic acid activates GPR40/FFA1 and phospholipase C to increase Ca2+i release and insulin secretion in islet beta-cells / 中国医学科学杂志(英文版)
Chinese Medical Sciences Journal
;
(4): 18-23, 2012.
Article
in English
| WPRIM
| ID: wpr-243273
ABSTRACT
<p><b>OBJECTIVE</b>To elucidate GPR40/FFA1 and its downstream signaling pathways in regulating insulin secretion.</p><p><b>METHODS</b>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 beta-cells by Fluo-3 intensity under confocal microscopy recording. Downregulation of GPR40/FFA1 expression by antisense oligonucleotides was performed in pancreatic beta-cells, and insulin secretion was assessed by enzyme-linked immunosorbent assay.</p><p><b>RESULTS</b>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 beta-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.</p><p><b>CONCLUSION</b>LA activates GPR40/FFA1 and PLC to stimulate Ca2+ release, resulting in an increase in [Ca2+]i and insulin secretion in rat islet beta-cells.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Type C Phospholipases
/
Physiology
/
Calcium
/
Rats, Sprague-Dawley
/
Bodily Secretions
/
Linoleic Acid
/
Receptors, G-Protein-Coupled
/
Enzyme Activation
/
Insulin-Secreting Cells
Limits:
Animals
Language:
English
Journal:
Chinese Medical Sciences Journal
Year:
2012
Type:
Article
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