Involvement of nitric oxide in neuroglycopenia-induced insulin and glucagon secretion in the mouse.
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, NG-nitro-L-arginine methyl ester (50 mg/kg) to conscious mice. It was found that NG-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, NG-nitro-L-arginine, which is devoid of the anticholinergic property of NG-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 NG-nitro-L-arginine methyl ester, NG-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 NG-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 micrograms/kg), were not influenced by NG-nitro-L-arginine methyl ester, NG-nitro-D-arginine methyl ester or NG-nitro-L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood; D002908:Chronic Disease; D003847:Deoxyglucose / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D007003:Hypoglycemia / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D013268:Stimulation, Chemical
D001786:Blood Glucose; D002395:Catecholamines; D007328:Insulin; D019335:Nitroarginine; D009569:Nitric Oxide; D002217:Carbachol; D001120:Arginine; D003847:Deoxyglucose; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester