THE NITRIC-OXIDE SYNTHASE-II INHIBITOR NG-NITRO-L-ARGININE STIMULATES PANCREATIC-ISLET INSULIN RELEASE INVITRO, BUT NOT IN THE PERFUSED PANCREAS

The effects of L-arginine and its derivatives N(G)-methyl-L-arginine (Meth-arg) and N(G)-nitro-L-arginine (Nit-arg) on the insulin release and glucose oxidation of isolated rat islets were investigated to evaluate possible influences of nitric oxide. Also, the insulin release and flow distribution within the perfused rat pancreas were studied in response to these agents. Arginine, Meth-arg, and Nit-arg stimulated insulin release in cultured islets, but had no effect on glucose oxidation. Arginine and Meth-arg, an inhibitor of the enzyme nitric oxide synthase I (NS-I) stimulated insulin release from the perfused pancreas. Nit-arg, however, which inhibits nitric oxide synthase II (NS-II) had no such effect. Neither arginine nor Nit-arg or Met-arg changed the distribution of microspheres within the perfused pancreas. We conclude that interference with NS type I or II has no effect on insulin release from cultured islets, but inhibition of NS-II abolishes the insulin response in the perfused pancreas, which may be mediated by factors released from endothelial cells. These effects are not due to any changes in the flow distribution within the pancreas. The lack of inhibitory effect by Nit-arg in cultured islets may reflect the absence of endothelial or nervous cells in the cultured islets.