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

Wang, Li, Zhao, Yufeng, Gui, Baosong, Fu, Rongguo, Ma, Feng, Yu, Jun, Qu, Ping, Dong, Lei and Chen, Chen (2011) Acute stimulation of glucagon secretion by linoleic acid results from GPR40 activation and [Ca2+](i) increase in pancreatic islet alpha-cells. Journal of Endocrinology, 210 2: 173-179.


Author Wang, Li
Zhao, Yufeng
Gui, Baosong
Fu, Rongguo
Ma, Feng
Yu, Jun
Qu, Ping
Dong, Lei
Chen, Chen
Title Acute stimulation of glucagon secretion by linoleic acid results from GPR40 activation and [Ca2+](i) increase in pancreatic islet alpha-cells
Formatted title Acute stimulation of glucagon secretion by linoleic acid results from GPR40 activation and [Ca2+]i increase in pancreatic islet α-cells
Journal name Journal of Endocrinology   Check publisher's open access policy
ISSN 0022-0795
1479-6805
Publication date 2011-08
Sub-type Article (original research)
DOI 10.1530/JOE-11-0132
Volume 210
Issue 2
Start page 173
End page 179
Total pages 7
Place of publication Bristol, United Kingdom
Publisher BioScientifica
Collection year 2012
Language eng
Formatted 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, itwas
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
([Ca2+]i) in identified rat α-cells, which is reflected
by increased Fluo-3 intensity under confocal microscopy
recording. The increase in [Ca2+]i was partly inhibited
by removal of extracellular Ca2+ and eliminated overall by
further exhaustion of intracellular Ca2+ stores using thapsigargin
treatment, suggesting that both Ca2+ release and Ca2+
influx contributed to the LA-stimulated increase in [Ca2+]i
in α-cells. Double immunocytochemical stainings showed
that GPR40 was expressed in glucagon-positive α-cells.
LA-stimulated increase in [Ca2+]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 [Ca2+]i by
LA. It is concluded that LA activates GPR40 and phospholipase
C (and downstream signaling pathways) to increase
Ca2+ release and associated Ca2+ influx through Ca2+ channels,
resulting in increase in [Ca2+]i and glucagon secretion.
Keyword Free Fatty-Acids
Impaired Glucose-Tolerance
Beta-Cell
Insulin-Secretion
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biomedical Sciences Publications
 
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