Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy

Nat Med. 1996 Dec;2(12):1344-7. doi: 10.1038/nm1296-1344.


Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) is a disorder of childhood associated with inappropriate hypersecretion of insulin by the pancreas. The pathogenesis of the condition has hitherto remained controversial. We show here that insulin-secreting cells from a homogeneous group of five infants with PHHI lack ATP-sensitive K+ channel (KATP) activity. As a consequence, PHHI beta-cells are spontaneously electrically active with high basal cytosolic Ca2+ concentrations due to Ca2+ influx. Our findings define the pathogenesis of this disease as a novel K+ channel disorder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters*
  • Action Potentials
  • Adenosine Triphosphate / physiology*
  • Calcium Channel Blockers / pharmacology
  • Cells, Cultured
  • Humans
  • Hyperinsulinism / metabolism*
  • Hypoglycemia / blood
  • Hypoglycemia / metabolism*
  • Infant, Newborn
  • Islets of Langerhans / physiology*
  • Potassium Channels / metabolism*
  • Potassium Channels, Inwardly Rectifying*
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Verapamil / pharmacology


  • ATP-Binding Cassette Transporters
  • Calcium Channel Blockers
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Drug
  • Sulfonylurea Receptors
  • Adenosine Triphosphate
  • Verapamil