[PDF][PDF] Acute stimulation of glucagon secretion by linoleic acid results from GPR40 activation and [Ca2+] i increase in pancreatic islet a-cells

L Wang, Y Zhao, B Gui, R Fu, F Ma, J Yu, P Qu… - J …, 2011 - researchgate.net
L Wang, Y Zhao, B Gui, R Fu, F Ma, J Yu, P Qu, L Dong, C Chen
J Endocrinol, 2011researchgate.net
The role of free fatty acids (FFAs) in glucagon secretion has not been well established, and
the involvement of FFA receptor GPR40 and its downstream signaling pathways in
regulating glucagon secretion are rarely demonstrated. In this study, it was found that
linoleic acid (LA) acutely stimulated glucagon secretion from primary cultured rat pancreatic
islets. LA at 20 and 40 mmol/l dose-dependently increased glucagon secretion both at 3
mmol/l glucose and at 15 mmol/l glucose, although 15 mmol/l glucose reduced basal …
Abstract
The role of free fatty acids (FFAs) in glucagon secretion has not been well established, and the involvement of FFA receptor GPR40 and its downstream signaling pathways in regulating glucagon secretion are rarely demonstrated. In this study, it was found that linoleic acid (LA) acutely stimulated glucagon secretion from primary cultured rat pancreatic islets. LA at 20 and 40 mmol/l dose-dependently increased glucagon secretion both at 3 mmol/l glucose and at 15 mmol/l glucose, although 15 mmol/l glucose reduced basal glucagon levels. LA induced an increase in cytoplasmic free calcium concentrations ([Ca2C] i) in identified rat a-cells, which is reflected by increased Fluo-3 intensity under confocal microscopy recording. The increase in [Ca2C] i was partly inhibited by removal of extracellular Ca2C and eliminated overall by further exhaustion of intracellular Ca2C stores using thapsigargin treatment, suggesting that both Ca2C release and Ca2C influx contributed to the LA-stimulated increase in [Ca2C] i in a-cells. Double immunocytochemical stainings showed that GPR40 was expressed in glucagon-positive a-cells. LA-stimulated increase in [Ca2C] i was blocked by inhibition of GPR40 expression in a-cells after GPR40-specific antisense treatment. The inhibition of phospholipase C activity by U73122 also blocked the increase in [Ca2C] i by LA. It is concluded that LA activates GPR40 and phospholipase C (and downstream signaling pathways) to increase Ca2C release and associated Ca2C influx through Ca2C channels, resulting in increase in [Ca2C] i and glucagon secretion.
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