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

Bo Ahrén, Sven Karlsson, Anton J.W. Scheurink, Anton B. Steffens

OnderzoeksoutputAcademicpeer review

8 Citaten (Scopus)

Samenvatting

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 mu g/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.

Originele taal-2English
Pagina's (van-tot)27-35
Aantal pagina's9
TijdschriftEuropean Journal of Pharmacology
Volume280
Nummer van het tijdschrift1
StatusPublished - 23-jun-1995

Citeer dit