title: Dependence on NADH produced during glycolysis for beta-cell glucose signaling.
abstract: An increase in cytosolic ATP following glucose metabolism by pancreatic beta-cells is the key signal initiating insulin secretion by causing blockade of ATP-dependent K+ channels (KATP). This induces membrane depolarization, leading to an elevation in cytosolic Ca2+ ([Ca2+]i) and insulin secretion. In this report we identify the critical metabolic step by which glucose initiates changes in beta-cell KATP channel activity, membrane potential, and [Ca2+]i. The signal stems from the glycolytic production of NADH during the oxidation of glyceraldehyde 3-phosphate, which is subsequently processed into ATP by mitochondria via the operation of discrete shuttle systems.
authors.affiliation: Glaxo Research Institute, Research Triangle Park, North Carolina 27709.
authors.forename: I D
authors.initials: ID
authors.lastname: Dukes
authors.forename: M S
authors.initials: MS
authors.lastname: McIntyre
authors.forename: R J
authors.initials: RJ
authors.lastname: Mertz
authors.forename: L H
authors.initials: LH
authors.lastname: Philipson
authors.forename: M W
authors.initials: MW
authors.lastname: Roe
authors.forename: B
authors.initials: B
authors.lastname: Spencer
authors.forename: J F
authors.initials: JF
authors.lastname: Worley
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D005986:Glyceraldehyde 3-Phosphate / Q000378:metabolism; D006019:Glycolysis; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009243:NAD / Q000378:metabolism*; D009536:Niacinamide / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015221:Potassium Channels; D009243:NAD; D005986:Glyceraldehyde 3-Phosphate; D009536:Niacinamide; D000255:Adenosine Triphosphate; D005947:Glucose; D002118:Calcium