Nitric oxide, islet acid glucan-1,4-alpha-glucosidase activity and nutrient-stimulated insulin secretion

The mechanism of nutrient-evoked insulin release is clearly complex. One pa rt of that mechanism is postulated to be the activation of the glycogenolyt ic enzyme acid glucan-1,4-alpha-glucosidase. As nitric oxide (NO) has been found to be a potent inhibitor of glucose-stimulated insulin secretion, we have now investigated a possible influence of exogenous NO and inhibition o f endogenous NO production on islet acid glucan-1,4-alpha-glucosidase activ ity in relation to insulin release stimulated by glucose and L-arginine. In isolated islets, NO derived from the intracellular NO donor hydroxylamine inhibited the activation of acid glucan-1,4-alpha-glucosidase and its isofo rm acid alpha-glucosidase in parallel with inhibition of glucose-stimulated insulin release. In comparison, other lysosomal enzymes were largely unaff ected. Similarly, the spontaneous NO donor sodium nitroprusside, as well as NO gas, when added to islet homogenates, suppressed the activities of thes e acid alpha-glucosidehydrolases and, to a lesser extent, the activities of other lysosomal enzymes. Finally, in the presence of the NO synthase inhib itor NO-nitro-L-arginine methyl ester, insulin release from isolated islets stimulated by glucose or L-arginine was markedly potentiated in parallel w ith an accompanying increase in the activities of acid glucan-1,4-a-glucosi dase and acid a-glucosidase. Other lysosomal enzymes and neutral a-glucosid ase were not influenced. We propose that an important inhibitory effect of NO on the insulin secretory processes stimulated by glucose and L-arginine is exerted via inactivation of islet acid glucan-1,4-alpha-glucosidase, a p utative key enzyme in nutrient-stimulated insulin release.