title: Adenosine triphosphate-sensitive potassium (K(ATP)) channel activity is coupled with insulin resistance in obesity and type 2 diabetes mellitus.
abstract: 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.
authors.affiliation: Diabetes Center, Tokyo Women's Medical University School of Medicine.
authors.forename: Taro
authors.initials: T
authors.lastname: Wasada
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000214:Acyl Coenzyme A / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006595:Hexosamines / Q000096:biosynthesis; D006706:Homeostasis; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D006949:Hyperlipidemias / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D007511:Ischemia / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D064233:Sulfonylurea Receptors
chemical_list: D018528:ATP-Binding Cassette Transporters; D000214:Acyl Coenzyme A; D005227:Fatty Acids; D006595:Hexosamines; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate; D005947:Glucose