SIGNAL-TRANSDUCTION IN ISLET HORMONE-RELEASE - INTERACTION OF NITRIC-OXIDE WITH BASAL AND NUTRIENT-INDUCED HORMONE RESPONSES

We examined the relation between the islet NO system and islet hormone secretion induced by either the non-glucose nutrient alpha-ketoisocap roic acid (KIC) or, in some experiments, glucose. KIC dose dependently stimulated insulin but inhibited glucagon secretion. In a medium devo id of any nutrient, the NO synthase (NOS)-inhibitor N-G nitro-L-argini ne methyl ester (L-NAME) induced an increase in basal insulin release but a decrease in glucagon release. These effects were evident also in K(+-)depolarised islets. KIC-induced insulin release was increased by L-NAME. This increase was abolished in K+-depolarised islets. in cont rast, glucose- induced insulin release was potentiated by L-NAME after K+ depolarisation. The intracellular NO donor hydroxylamine dose depe ndently inhibited KIC-stimulated insulin release and reversed KIC-indu ced suppression of glucagon release. Our data suggest that islet hormo ne secretion in a medium devoid of nutrients is greatly affected by th e islet NO system, whereas KIC-induced secretion is little affected. G lucose-induced insulin release, however, is accompanied by increased N OS activity, the NOS-activating signal being derived from the glycolyt ic-pentose shunt part of glucose metabolism. The observed NO effects o n islet hormone release can proceed independently of membrane-depolari sation events. (C) 1998 Elsevier Science Inc.