Elevation in Intracellular Long-Chain Acyl-Coenzyme A Esters Lead to Reduced β-Cell Excitability via Activation of Adenosine 5′-Triphosphate-Sensitive Potassium Channels

摘要: Closure of pancreatic beta-cell ATP-sensitive potassium (K(ATP)) channels links glucose metabolism to electrical activity and insulin secretion. It is now known that saturated, but not polyunsaturated, long-chain acyl-coenyzme A esters (acyl-CoAs) can potently activate K(ATP) when superfused directly across excised membrane patches, suggesting a plausible mechanism account for reduced excitability secretion observed in obesity type 2 diabetes. However, due elevation endogenous saturated acyl-CoAs has been confirmed intact beta-cells. To test this notion directly, acyl-CoA levels were elevated within primary mouse beta-cells using virally delivered overexpression synthetase-1 (AdACSL-1), the effects on channel cell was assessed perforated whole-cell cell-attached patch-clamp technique. Data indicated significant increase AdACSL-1-infected cultured medium supplemented with palmitate/oleate polyunsaturated fat linoleate. No changes ATP/ADP ratio any groups. Furthermore, (with palmitate/oleate) showed decrease responsiveness tolbutamide hyperpolarized resting potential at 5 mm glucose. These results suggest direct link between intracellular fatty ester accumulation activation, which may contribute dysfunction