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

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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 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.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalEuropean Journal of Pharmacology
Volume280
Issue number1
Publication statusPublished - 23-Jun-1995

Keywords

  • INSULIN SECRETION
  • GLUCAGON SECRETION
  • NEUROGLYCOPENIA
  • 2-DEOXY-D-GLUCOSE
  • NITRIC OXIDE (NO)
  • NITRIC OXIDE SYNTHASE
  • N-G-NITRO-L-ARGININE METHYL ESTER
  • N-G-NITRO-L-ARGININE
  • (MOUSE)
  • RECEPTOR ANTAGONISTS
  • GUANYLATE-CYCLASE
  • RAT ISLETS
  • ARGININE
  • ENDOTHELIUM
  • INHIBITION
  • SYNTHASE
  • RELEASE
  • LANGERHANS
  • MECHANISM

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