KATP channel mutations in congenital hyperinsulinism

Semin Pediatr Surg. 2011 Feb;20(1):18-22. doi: 10.1053/j.sempedsurg.2010.10.012.

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.

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics*
  • Congenital Hyperinsulinism / diagnosis
  • Congenital Hyperinsulinism / genetics*
  • Congenital Hyperinsulinism / therapy
  • Diazoxide / pharmacology
  • Humans
  • KATP Channels / genetics*
  • Mutation*
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Receptors, Drug / genetics*
  • Sulfonylurea Receptors
  • Vasodilator Agents / pharmacology

Substances

  • ATP-Binding Cassette Transporters
  • KATP Channels
  • Kir6.2 channel
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Vasodilator Agents
  • Diazoxide