Involvement of nitric oxide in neuroglycopenia-induced insulin and glucagon secretion in the mouse

Abstract

Neuroglycopenia induced by administration of 2-deoxy- d-glucose is known 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 involved in this process. Therefore, 2-deoxy- d-glucose (500 mg/kg) was injected 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, inhibited 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 stereoisomer of N G-nitro- l-arginine methyl ester, N G-nitro- d-arginine methyl ester, which is devoid of NO synthase inhibitory activity, was without effect on 2-deoxy- d-glucose-induced insulin and glucagon secretion. Plasma levels of adrenaline and noradrenaline after administration of 2-deoxy- d-glucose were also reduced by N G-nitro- l-arginine methyl ester. In contrast, the insulin and glucagon secretory responses to intravenous injection of arginine (250 mg/kg), glucose (500 mg/kg) or the cholinergic agonist, carbachol (30 μg/kg), were not influenced by N G-nitro- 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 insulin and glucagon during neuroglycopenia in the mouse is partially mediated by NO.