title: Mechanisms of amino acid-stimulated insulin secretion in congenital hyperinsulinism.
abstract: The role of amino acids in the regulation of insulin secretion in pancreatic beta-cells is highlighted in three forms of congenital hyperinsulinism (HI), namely gain-of-function mutations of glutamate dehydrogenase (GDH), loss-of-function mutations of ATP-dependent potassium channels, and a deficiency of short-chain 3-hydroxyacyl-CoA dehydrogenase. Studies on disease mouse models of HI suggest that amino acid oxidation and signaling effects are the major mechanisms of amino acid-stimulated insulin secretion. Amino acid oxidation via GDH produces ATP and triggers insulin secretion. The signaling effect of amino acids amplifies insulin release after beta-cell depolarization and elevation of cytosolic calcium.
authors.affiliation: Division of Endocrinology, Department of Pediatrics, The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.forename: Changhong
authors.initials: C
authors.lastname: Li
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000235:genetics; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D044903:Congenital Hyperinsulinism / Q000378:metabolism*; D005969:Glutamate Dehydrogenase / Q000235:genetics; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D009154:Mutation; D010084:Oxidation-Reduction; D015221:Potassium Channels / Q000235:genetics; D015398:Signal Transduction; D019076:Transgenes
chemical_list: D000596:Amino Acids; D007328:Insulin; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D015094:3-Hydroxyacyl CoA Dehydrogenases; D005969:Glutamate Dehydrogenase