Nitric oxide (nitrogen monoxide, NO) stimulates insulin secretion by inducing calcium release from mitochondria.
Nitric oxide (nitrogen monoxide, NO) acts as messenger molecule in a variety of cells and may also be involved in the insulin secretory pathway of islet beta-cells. We report here that NO at a low micromolar concentration stimulates epinephrine-sensitive insulin secretion from cells of the beta-cell line, INS-1. Insulin secretion is paralleled by a reversible decrease of the mitochondrial membrane potential and by an increase of the cytosolic calcium. Chelation of intracellular, but not of extracellular calcium prevents the NO-induced insulin secretion. These data indicate that NO can stimulate insulin secretion by deenergizing mitochondria and thereby triggering mitochondrial calcium release.
Laffranchi
R
R
Department of Internal Medicine, University Hospital Zürich, Switzerland.
Gogvadze
V
V
Richter
C
C
Spinas
G A
GA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002460:Cell Line; D004837:Epinephrine / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007425:Intracellular Membranes / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000502:physiology*; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D015398:Signal Transduction; D014475:Uncoupling Agents / Q000494:pharmacology
D007328:Insulin; D014475:Uncoupling Agents; D009569:Nitric Oxide; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D002118:Calcium; D004837:Epinephrine