Activation of ATP-sensitive potassium channels in rat pancreatic th p a 31

au) were observed in primary cultured rat pancreatic b-cells. LA (20 mM) induced hyperpolarization of MP and opening of hyperpolarization of MP by activating KATP channels via both intracellular metabolites and activation of GPR40. It indicates secretion, FFAs substantially decreases glucose-stimulated activation of GPR40 induces an increase in intracellular opening and closure of voltage-dependent calcium channels via calcium-dependent inactivation pathway in rat b-cells 533Journal of Endocrinology (2008) 198, 533–540calcium concentration and insulin secretion (Briscoe et al. 2003, Fujiwara et al. 2005). On the other hand, intracellular metabolism and the generation of lipid-derived signal (Feng et al. 2008). However, the effects of LA on MP and KATP channel activity are not clarified. In this study, we first observed the effects of LA on MP. Surprisingly, we found that DOI: 10.1677/JOE-08-0105insulin secretion (GSIS) under a long-term treatment condition (Zraika et al. 2002). The discovery that FFAs activate the G-protein-coupled membrane receptor, GPR40, gives an explanation of how FFAs acutely stimulate insulin secretion (Briscoe et al. 2003, Itoh et al. 2003, Shapiro et al. 2005). GPR40 is abundantly expressed in b-cells, and and other voltage-dependent channels. There is evidence that linoleic acid (LA) influences the action of voltage-dependent potassium channels on the membrane of rat pancreatic b-cells via GPR40 and the cAMP and protein kinase A (PKA) intracellular signalling system (Feng et al. 2006). In addition, it is found that LA inhibits voltage-dependent calcium channelsHaber et al. 2006). FFAs have multiple effects on pancreatic b-cells, including inducing apoptosis and stimulating insulin secretion. Although exogenous FFAs stimulate insulin ation of membrane potential (MP) and bursting of action potentials when stimulated by glucose (Rorsman 1997). MP is very important to insulin secretion because it determines thetolbutamide, a KATP channel blocker. Inhibition of LA metabolism by acyl-CoA synthetase inhibitor, triacsin C (10 mM), partially inhibited LA-induced opening of KATP channels by 64%. The non-FFA G protein-coupled recepto