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 part of that mechanism is postulated to be the activation of the glycogenolytic 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 of endogenous NO production on islet acid glucan-1,4-alpha-glucosidase activity 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 isoform acid alpha-glucosidase in parallel with inhibition of glucose-stimulated insulin release. In comparison, other lysosomal enzymes were largely unaffected. Similarly, the spontaneous NO donor sodium nitroprusside, as well as NO gas, when added to islet homogenates, suppressed the activities of these acid alpha-glucosidehydrolases and, to a lesser extent, the activities of other lysosomal enzymes. Finally, in the presence of the NO synthase inhibitor N(G)-nitro-l-arginine methyl ester, insulin release from isolated islets stimulated by glucose or l-arginine was markedly potentiated in parallel with an accompanying increase in the activities of acid glucan-1,4-alpha-glucosidase and acid alpha-glucosidase. Other lysosomal enzymes and neutral alpha-glucosidase 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 putative key enzyme in nutrient-stimulated insulin release.
Mosén
H
H
Institute of Physiological Sciences, Department of Pharmacology, University of Lund, Sweden. henrik.mosen@farm.lu.se
Salehi
A
A
Lundquist
I
I
D000818:Animals; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D005087:Glucan 1,4-alpha-Glucosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors; D019811:Hydroxylamine / Q000494:pharmacology; D007515:Islets of Langerhans / Q000201:enzymology*; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000378:metabolism
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D020030:Nitric Oxide Donors; D009599:Nitroprusside; D019811:Hydroxylamine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000520:alpha-Glucosidases; D005087:Glucan 1,4-alpha-Glucosidase; D019331:NG-Nitroarginine Methyl Ester