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

Familial hyperinsulinism, also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI), is a genetic disease characterized by mild to severe 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 (KATP channel) present in the plasma membrane of pancreatic beta-cells. This channel is formed by two subunits, the high-affinity sulfonylurea receptor, SUR1, and KIR6.2, a member of the inwardly rectifying family of K+ channels. KATP channels regulate insulin secretion by linking membrane excitability with glucose metabolism. Approximately 50 mutations, in both channel subunits, that abolish or alter the regulation of beta-cell KATP channels have been identified in patients with the recessive form of PHHI.