title: KATP channel mutations in congenital hyperinsulinism.
abstract: Adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP) channels) have a central role in the regulation of insulin secretion in pancreatic β cells. They are octameric complexes organized around the central core constituted by the Kir6.2 subunits. The regulation of the channel itself takes place on the sulfonylurea receptor-1 subunit. The channel opens and closes according to the balance between adenine nucleotide ATP and adenosine diphosphate. Hyperinsulinemic hypoglycemia (also named congenital hyperinsulinism, or CHI) is associated with loss-of-function K(ATP) channel mutations. Their frequency depends on the histopathological form and the responsiveness of CHI patients to diazoxide. ABCC8/KCNJ11 defects are identified in approximately 80% of patients with CHI refractory to diazoxide. Within this group, focal forms are related to a paternally inherited KCNJ11 or ABCC8 mutation and the loss of the corresponding maternal allele in some pancreatic β cells leading to a focal lesion. Diffuse forms are mostly associated with recessively inherited mutations. Some patients with diffuse forms also carried a single K(ATP) channel mutation. In contrast, K(ATP) mutations are involved in 15% of diazoxide-responsive CHI cases that are either sporadic or dominantly inherited.
authors.affiliation: Department of Genetics, AP-HP Hôpital Pitié-Salpétrière, Université Pierre et Marie Curie, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Saint-Martin
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Arnoux
authors.forename: Pascale
authors.initials: P
authors.lastname: de Lonlay
authors.forename: Christine
authors.initials: C
authors.lastname: Bellanné-Chantelot
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D044903:Congenital Hyperinsulinism / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D003981:Diazoxide / Q000494:pharmacology; D006801:Humans; D054086:KATP Channels / Q000235:genetics*; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D064233:Sulfonylurea Receptors; D014665:Vasodilator Agents / Q000494:pharmacology; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D003981:Diazoxide; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014665:Vasodilator Agents; D000099161:Kcnj11 Channel