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.