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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-08-0105v1 198/3/533    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhao, Y.-F. Articles by Chen, C. Search for Related Content PubMed PubMed Citation Articles by Zhao, Y.-F. Articles by Chen, C.

Y Zhao, SBMS, University of Queensland, Brisbane, Australia
J Pei, Physiology, Fourth Military Medical University, Xian, China
C Chen, Endocrine Cell Biology, Prince Henry's Institute, Clayton, 3169, Australia

Correspondence: Chen Chen, Email: chen.chen{at}uq.edu.au

Abstract

ATP-sensitive potassium channels (KATP channels) determine the excitability of pancreatic β-cells and importantly regulate glucose-stimulated insulin secretion (GSIS). Long-chain free fatty acids (FFAs) decrease GSIS after long term exposure to β-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 β-cells. LA (20 µM) induced hyperpolarization of MP and opening of KATP channels, which was totally reversed and inhibited by tolbutamide, a KATP channel blocker. Inhibition of LA metabolism by acyl-CoA synthetase inhibitor, triacsin C (10 µM), partially inhibited LA-induced opening of KATP channels by 64%. The non-FFA GPR40 agonist, GW9508 (40 µM), induced an opening of KATP channels, which was similar to that induced by LA under triacsin C treatment. Blockade of protein kinase A and protein kinase 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 KATP 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 β-cell dysfunction induced by FFAs.