Does nitric oxide play a role in stimulus-secretion and/or synthesis-secretion coupling of insulin?
By using the perfused rat pancreas model and the nitric oxide synthase inhibitor, nitro-arginine methyl ester (NAME), we examined the hypothesis that first-phase potentiation or second-phase inhibition of insulin release due to the amino acid arginine (or both) are the result of its conversion to nitric oxide (NO). In the presence of 16.7 mM glucose, 20 mM arginine caused a first-phase potentiation of insulin release when compared with glucose controls, while inhibiting the second-phase insulin release. When 20 mM NAME was added in addition to 20 mM arginine and 16.7 mM glucose, the total insulin released during the first secretory phase was not significantly different from that of the glucose plus arginine group, suggesting that inhibition of NO production does not affect arginine-potentiated first-phase insulin release. Similarly, the presence of NAME failed to reverse the arginine inhibition of second-phase insulin release. The presence of NAME resulted in a more pronounced inhibition of insulin secretion. Correspondingly, compared with the glucose-only controls, the presence of 20 mM NAME plus 16.7 mM glucose resulted in a significant decrease in insulin release during the second phase, whereas the presence of NAME did not affect first-phase glucose-stimulated insulin release. Thus we conclude that the conversion of arginine to nitric oxide does not play a significant role in glucose-stimulated first-phase potentiation or second-phase inhibition of insulin release due to arginine.
Strandgaard
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Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis 95616, USA.
Curry
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D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D007700:Kinetics; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester