INVOLVEMENT OF NITRIC-OXIDE IN NEUROGLYCOPENIA-INDUCED INSULIN AND GLUCAGON-SECRETION IN THE MOUSE

Neuroglycopenia induced by administration of 2-deoxy-D-glucose is know n to stimulate the secretion of both insulin and glucagon in mice by a mechanism that is dependent on neural activity. In the present study, we examined whether the neurotransmitter nitric oxide (NO) is involve d in this process. Therefore, 2-deoxy-D-glucose (500 mg/kg) was inject ed intravenously alone or together with the inhibitor of NO synthase, N-G-nitro-L-arginine methyl ester (50 mg/kg) to conscious mice. It was found that N-G-nitro-L-arginine methyl ester inhibited the increased plasma levels of both insulin (by 26%; P = 0.039) and glucagon (by 45% ; P < 0.001) at 10 min after injection of 2-deoxy-D-glucose. Similarly , the NO synthase inhibitor, N-G-nitro-L-arginine, which is devoid of the anticholinergic property of N-G-nitro-L-arginine methyl ester, inh ibited the responses of both insulin (by 53%; P = 0.026) and glucagon (by 57%; P = 0.003) to 2-deoxy-D-glucose. In contrast, the stereoisome r of N-G-nitro-L-arginine methyl ester, N-G-nitro-D-arginine methyl es ter, which is devoid of NO synthase inhibitory activity, was without e ffect on 2-deoxy-D-glucose-induced insulin and glucagon secretion. Pla sma levels of adrenaline and noradrenaline after administration of 2-d eoxy-D-glucose were also reduced by N-G-nitro-L-arginine methyl ester. In contrast, the insulin and glucagon secretory responses to intraven ous injection of arginine (250 mg/kg), glucose (500 mg/kg) or the chol inergic agonist, carbachol (30 mu g/kg), were not influenced by N-G-ni tro-L-arginine methyl ester, N-G-nitro-D-arginine methyl ester or N-G- nitro-L-arginine. We conclude that the increased secretion of both ins ulin and glucagon during neuroglycopenia in the mouse is partially med iated by NO.