Insulin secretion from pancreatic B cells caused by L-arginine-derived nitrogen oxides.
L-arginine causes insulin release from pancreatic B cells. Data from three model systems support the hypothesis that L-arginine-derived nitrogen oxides (NOs) mediate insulin release stimulated by L-arginine in the presence of D-glucose and by the hypoglycemic drug tolbutamide. The formation of NO in pancreatic B cells was detected both chemically and by the NO-induced accumulation of guanosine 3',5'-monophosphate. NG-substituted L-arginine analogs inhibited the release of both insulin and NO. Protein immunoblot and histochemical analysis with antiserum to type I NO synthase suggest that the formation of NO in pancreatic B cells is catalyzed by an NADPH- (reduced form of nicotinamide adenine dinucleotide phosphate), Ca2+/calmodulin-dependent type I NO synthase of about 150 kilodaltons.
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
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Schmidt
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Warner
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Ishii
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Sheng
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Murad
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002147:Calmodulin / Q000494:pharmacology; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009589:Nitrogen Oxides / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D019323:omega-N-Methylarginine
D002147:Calmodulin; D007328:Insulin; D009589:Nitrogen Oxides; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009249:NADP; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D005947:Glucose; D002118:Calcium