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

We provide immunocytochemical evidence that the neuronal isoform of constit utive NO synthase (cNOS) is expressed in the rat insulinoma cell line INS-1 . Furthermore, using N omega -nitro-L-arginine methyl ester (L-NAME), a pha rmacological inhibitor of cNOS activity, we show that this enzyme is implic ated 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 in crease in insulin release, suggesting that cNOS exerts an inhibitory tone o n basal insulin secretion. Moreover, L-arginine, the physiological substrat e of cNOS, significantly reduced the marked enhancing effect Of L-NAME on i nsulin release and to a lesser extent, at low concentrations, that of 10 mM KC1. 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 neg ative modulation on insulin secretion in INS-1 cells, confirming the previo us results obtained in the isolated perfused rat pancreas or pancreatic isl ets. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.