Activation of ATP-sensitive potassium channels in rat pancreatic beta-cells by linoleic acid through both intracellular metabolites and membrane receptor signalling pathway

Zhao, Yu-Feng, Pei, Jianming and Chen, Chen (2008) Activation of ATP-sensitive potassium channels in rat pancreatic beta-cells by linoleic acid through both intracellular metabolites and membrane receptor signalling pathway. Journal of Endocrinology, 198 3: 533-540.


Author Zhao, Yu-Feng
Pei, Jianming
Chen, Chen
Title Activation of ATP-sensitive potassium channels in rat pancreatic beta-cells by linoleic acid through both intracellular metabolites and membrane receptor signalling pathway
Formatted title Activation of ATP-sensitive potassium channels in rat pancreatic ß-cells by linoleic acid through both intracellular metabolites and membrane receptor signalling pathway
Journal name Journal of Endocrinology   Check publisher's open access policy
ISSN 0022-0795
Publication date 2008-09
Year available 2008
Sub-type Article (original research)
DOI 10.1677/JOE-08-0105
Volume 198
Issue 3
Start page 533
End page 540
Total pages 7
Editor J. B. Davis
Place of publication The United Kingdom
Publisher Society for Endocrinology
Collection year 2009
Language eng
Subject C1
920106 Endocrine Organs and Diseases (excl. Diabetes)
11 Medical and Health Sciences
110999 Neurosciences not elsewhere classified
Abstract ATP-sensitive potassium channels (K-ATP channels) determine the excitability of pancreatic beta-cells and importantly regulate glucose-stimulated insulin secretion (GSIS). Long-chain free fatty acids (FFAs) decrease GSIS after long-term exposure to beta-cells, but the effects of exogenous FFAs on K-ATP channels are not yet well clarified. In this study, the effects of linoleic acid (LA) on membrane potential (MP) and K-ATP channels were observed in primary cultured rat pancreatic beta-cells. LA (20 mu M) induced hyperpolarization of MP and opening of K-ATP channels, which was totally reversed and inhibited by tolbutamide, a K-ATP channel blocker. Inhibition of LA metabolism by acyl-CoA synthetase inhibitor, triacsin C (10 mu M), partially inhibited LA-induced opening of K-ATP channels by 64%, The non-FFA G protein-coupled receptor (GPR) 40 agonist, GW9508 (40 mu M), induced an opening of K-ATP channels, which was similar to that induced by LA under triacsin C treatment. Blockade of protein kinases A and C did not influence the opening of K-ATP channels induced by LA and GW9508, indicating that these two protein kinase pathways are not involved in the action of LA on K-ATP channels. The present study demonstrates that LA induces hyperpolarization of MP by activating K-ATP channels via both intracellular metabolites and activation of GPR40. It indicates that not only intracellular metabolites of FFAs but also GPR40-mediated pathways take part in the inhibition of GSIS and beta-cell dysfunction induced by FFAs.
Formatted abstract ATP-sensitive potassium channels (KATP channels) determine the excitability of pancreatic  ß-cells and importantly regulate glucose-stimulated insulin secretion (GSIS). Long-chain free fatty acids (FFAs) decrease GSIS after long-term exposure to ß-cells, but the effects of exogenous FFAs on KATP channels are not yet well clarified. In this study, the effects of linoleic acid (LA) on membrane potential (MP) and KATP channels were observed in primary cultured rat pancreatic beta-cells. LA (20 mu M) induced hyperpolarization of MP and opening of KATP channels, which was totally reversed and inhibited by tolbutamide, a K-ATP channel blocker. Inhibition of LA metabolism by acyl-CoA synthetase inhibitor, triacsin C (10 mu M), partially inhibited LA-induced opening of KATP channels by 64%, The non-FFA G protein-coupled receptor (GPR) 40 agonist, GW9508 (40 mu M), induced an opening of KATP channels, which was similar to that induced by LA under triacsin C treatment. Blockade of protein kinases A and C did not influence the opening of KATP channels induced by LA and GW9508, indicating that these two protein kinase pathways are not involved in the action of LA on KATP channels. The present study demonstrates that LA induces hyperpolarization of MP by activating K-ATP channels via both intracellular metabolites and activation of GPR40. It indicates that not only intracellular metabolites of FFAs but also GPR40-mediated pathways take part in the inhibition of GSIS and beta-cell dysfunction induced by FFAs.
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Biomedical Sciences Publications
 
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