Adenosine triphosphate-sensitive potassium (KATP) channel activity is coupled with insulin resistance in obesity and type 2 diabetes mellitus

ATP sensitive potassium (K-ATP) channels reside in the plasma membrane of many excitable cells such as pancreatic beta-cells, heart, skeletal muscle and brain, where they link cellular metabolic energy to membrane electrical activity. They are composed of two subunits, K+ ion selective pore (Kir) and sulfonylurea receptor (SUR). In addition to the central role of pancreatic beta-cell K-ATP channels in glucose-mediated insulin secretion, several lines of evidence support the hypothesis that K-ATP channels modulate glucose transport in the insulin target tissues. Inhibition of K-ATP channels by glibenclamide or gliclazide or an increase in intracellular ATP during hyperglycemia (glucose effect) or exercise facilitates glucose utilization, while activation of the channels by potassium channel openers, hypothermia (cardiac surgery), or ischemic damage (myocardial and brain infarction) reduces glucose uptake induced by insulin or hyperglycemia. Because insulin action has been known to depend on the energy level of the target cells, K-ATP channel may function as an effector in this respect. It is now evident that long chain acyl-CoA esters, metabolically active forms of fatty acids, are the most potent and physiologically important activator of K-ATP channels. Thus, I suppose that the sustained activation of K-ATP channels by long chain fatty acyl-CoA seems to be a missing link between lipotoxicity and insulin resistance in obesity and type 2 diabetes mellitus.