A constitutive nitric oxide synthase modulates insulin secretion in the INS-1 cell line

• Published in: Molecular and cellular endocrinology 2001-10, Vol.183 (1), p.41-48
• Main Authors: Beffy, P, Lajoix, A.D, Masiello, P, Dietz, S, Péraldi-Roux, S, Chardès, T, Ribes, G, Gross, R
• Format: Article
• Language: English
• Subjects: Animals; Arginine - pharmacology; Enzyme Inhibitors - pharmacology; Glucose - pharmacology; INS-1 cells; Insulin - metabolism; Insulin Secretion; Insulinoma; Isoenzymes - metabolism; Life Sciences; Microscopy, Fluorescence; Neuronal nitric oxide synthase; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - metabolism; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type I; Pancreatic Neoplasms; Potassium Chloride - pharmacology; Rats; Succinates - pharmacology; Tumor Cells, Cultured
• ISSN: 0303-7207; 1872-8057; 0303-7207
• DOI: 10.1016/S0303-7207(01)00610-4

We provide immunocytochemical evidence that the neuronal isoform of constitutive NO synthase (cNOS) is expressed in the rat insulinoma cell line INS-1. Furthermore, using Nω-nitro- l-arginine methyl ester ( l-NAME), a pharmacological inhibitor of cNOS activity, we show that this enzyme is implicated in the modulation of insulin secretion in INS-1 cells. Indeed, in the presence of 2.8 mM glucose, l-NAME induced a specific and dose-dependent increase in insulin release, suggesting that cNOS exerts an inhibitory tone on basal insulin secretion. Moreover, l-arginine, the physiological substrate of cNOS, significantly reduced the marked enhancing effect of l-NAME on insulin release and to a lesser extent, at low concentrations, that of 10 mM KCl. l-NAME also potentiated the insulin secretion stimulated by 5.5 and 8.3 mM glucose, but in this case, its effect was not reduced by l-arginine. In conclusion, our data show that the neuronal isoform of cNOS exerts a negative modulation on insulin secretion in INS-1 cells, confirming the previous results obtained in the isolated perfused rat pancreas or pancreatic islets.