title: Loss of functional KATP channels in pancreatic beta-cells causes persistent hyperinsulinemic hypoglycemia of infancy.
abstract: 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.
authors.affiliation: Department of Biomedical Science, University of Sheffield, UK.
authors.forename: C
authors.initials: C
authors.lastname: Kane
authors.forename: R M
authors.initials: RM
authors.lastname: Shepherd
authors.forename: P E
authors.initials: PE
authors.lastname: Squires
authors.forename: P R
authors.initials: PR
authors.lastname: Johnson
authors.forename: R F
authors.initials: RF
authors.lastname: James
authors.forename: P J
authors.initials: PJ
authors.lastname: Milla
authors.forename: A
authors.initials: A
authors.lastname: Aynsley-Green
authors.forename: K J
authors.initials: KJ
authors.lastname: Lindley
authors.forename: M J
authors.initials: MJ
authors.lastname: Dunne
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000200:Action Potentials; D000255:Adenosine Triphosphate / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism*; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D014700:Verapamil / Q000494:pharmacology
chemical_list: D018528:ATP-Binding Cassette Transporters; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000255:Adenosine Triphosphate; D014700:Verapamil