K_ATP channelopathies in the pancreas

Adenosine-triphosphate-sensitive potassium channels (K_ATP) are regulated by adenosine nucleotides, and, thereby, couple cellular metabolism with electrical activity in multiple tissues including the pancreatic â-cell. The critical involvement of K_ATP in insulin secretion is confirmed by the demonstration that inactivating and activating mutations in K_ATP underlie persistent hyperinsulinemia and neonatal diabetes mellitus, respectively, in both animal models and humans. In addition, a common variant in K_ATP represents a risk factor in the etiology of type 2 diabetes. This review focuses on the mechanistic basis by which K_ATP mutations underlie insulin secretory disorders and the implications of these findings for successful clinical intervention.