Familial hyperinsulinism and pancreatic beta-cell ATP-sensitive potassium channels

Familial hyperinsulinism, also known as persistent hyperinsulinemic hypogly cemia of infancy (PHHI), is a genetic disease characterized by mild to seve re hypoglycemia in the presence of inappropriately high levels of insulin. The recessive form is caused by mutations in the adenosine 5'-triphosphate (ATP)-sensitive K+ channel (K-ATP channel) present in the plasma membrane o f pancreatic beta-cells. This channel is formed by two subunits, the high-a ffinity sulfonyl-urea receptor, SUR1, and K(1R)6.2, a member of the inwardl y rectifying family of K+ channels. K-ATP channels regulate insulin secreti on by linking membrane excitability with glucose metabolism. Approximately 50 mutations, in both channel subunits, that abolish or alter the regulatio n of beta-cell K-ATP channels have been identified in patients with the rec essive form of PHHI.