Activation of the ATP-sensitive K Channel by Long Chain Acyl-CoA A ROLE IN MODULATION OF PANCREATIC β-CELL GLUCOSE SENSITIVITY

摘要: Long-term exposure to elevated levels of long chain free fatty acids decreases glucose-induced insulin secretion from pancreatic islets and clonal beta-cells. The mechanism for this loss glucose sensitivity is at present not known. In study, we evaluated the possibility that increases in acyl-CoA esters (LC-CoA), metabolically active form acids, might mediate sensitivity. We observed cellular LC-CoA increased more than 100% response overnight incubation with 0.5 mM palmitic acid complexed albumin. same studies, total CoA pool by about 40%. Patch-clamp studies demonstrated saturated unsaturated LC-CoA, but malonyl-CoA or CoASH, induced a rapid slowly reversible opening ATP-sensitive K+ channels. effect was concentration-dependent between 10 nM 1 microM. These findings indicate ATP-regulated K/ channels sensitive target suggest high which accumulate hyperglycemia prolonged may prevent channel closure contribute development beta-cell insensitivity.