K(ATP) channelopathies in the pancreas.
Adenosine-triphosphate-sensitive potassium channels (KATP) are regulated by adenosine nucleotides, and, thereby, couple cellular metabolism with electrical activity in multiple tissues including the pancreatic beta-cell. The critical involvement of KATP in insulin secretion is confirmed by the demonstration that inactivating and activating mutations in KATP underlie persistent hyperinsulinemia and neonatal diabetes mellitus, respectively, in both animal models and humans. In addition, a common variant in KATP represents a risk factor in the etiology of type 2 diabetes. This review focuses on the mechanistic basis by which KATP mutations underlie insulin secretory disorders and the implications of these findings for successful clinical intervention.
Remedi
Maria S
MS
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA. mremedi@wustl.edu
Koster
Joseph C
JC
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology*; D000818:Animals; D053447:Channelopathies / Q000235:genetics / Q000503:physiopathology*; D044903:Congenital Hyperinsulinism / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000502:physiology*; D011955:Receptors, Drug / Q000235:genetics / Q000502:physiology*; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel