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.