GW9508 inhibits insulin secretion by activating ATP-sensitive potassium channels in rat pancreatic beta-cells

Zhao, Yu-Feng, Wang, Li, Zha, Dingjun, Qiao, Li, Lu, Lianjun, Yu, Jun, Qu, Ping, Sun, Qiang, Qiu, Jianhua and Chen, Chen (2013) GW9508 inhibits insulin secretion by activating ATP-sensitive potassium channels in rat pancreatic beta-cells. Journal of Molecular Endocrinology, 51 1: 69-77. doi:10.1530/JME-13-0019


Author Zhao, Yu-Feng
Wang, Li
Zha, Dingjun
Qiao, Li
Lu, Lianjun
Yu, Jun
Qu, Ping
Sun, Qiang
Qiu, Jianhua
Chen, Chen
Title GW9508 inhibits insulin secretion by activating ATP-sensitive potassium channels in rat pancreatic beta-cells
Formatted title
Gw9508 inhibits insulin secretion by activating ATP-sensitive potassium channels in rat pancreatic β-cells
Journal name Journal of Molecular Endocrinology   Check publisher's open access policy
ISSN 0952-5041
1479-6813
Publication date 2013-08
Sub-type Article (original research)
DOI 10.1530/JME-13-0019
Volume 51
Issue 1
Start page 69
End page 77
Total pages 9
Place of publication Woodlands, Bristol, United Kingdom
Publisher BioScientifica
Collection year 2014
Language eng
Formatted abstract
GW9508 is an agonist of G protein-coupled receptor 40 (GPR40) that is expressed in pancreatic β-cells and is reported to regulate insulin secretion. However, the effects of GW9508 on pancreatic β-cells in primary culture have not been well investigated. This study measured the acute effects of GW9508 on insulin secretion from rat pancreatic islets in primary culture, and the insulin secretion-related events such as the changes in membrane potential, ATP-sensitive potassium currents (KATP currents), and intracellular Ca2+ concentrations ([Ca2+]i) of rat islet β-cells were also recorded. GW9508 (10–40 μM) did not influence basal insulin levels at 2 mM glucose, but it (above 20 μM) significantly inhibited 5 and 15 mM glucose-stimulated insulin secretion (GSIS). GW9508 did not inhibit insulin secretion stimulated by tolbutamide, the closer of KATP channels. GW9508 activated KATP channels and blocked the membrane depolarization and the increase in [Ca2+]i that were stimulated by glucose. GW9508 itself stimulated a transient increase in [Ca2+]i, which was fully blocked by depletion of intracellular Ca2+ stores with thapsigargin or by inhibition of phospholipase C (PLC) activity with U73122. GW9508-induced activation of KATP channels was only partly inhibited by U73122 treatment. In conclusion, although it stimulates a transient release of Ca2+ from intracellular Ca2+ stores via activation of PLC, GW9508 inhibits GSIS by activating KATP channels probably in a distal step to GPR40 activation in rat β-cells.
Keyword GW9508
Insulin
K-ATP channels
beta-Cells
Agonist recognition
Signaling pathways
Receptor GPR40
Islet cells
Fatty-acids
Glucose
Mouse
Release
Ca2+
Electrophysiology
β-Cells
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
 
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