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 N omega -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 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 negative modulation on insulin secretion in INS-1 cells, confirming the previous results obtained in the isolated perfused rat pancreas or pancreatic islets. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.
|Autori interni:||MASIELLO, PELLEGRINO|
|Autori:||Beffy P; Lajoix AD; Masiello P; Dietz S; Peraldi-Roux S; Chardes T; Ribes G; Gross R|
|Titolo:||A constitutive nitric oxide synthase modulates insulin secretion in the INS-1 cell line|
|Anno del prodotto:||2001|
|Digital Object Identifier (DOI):||10.1016/S0303-7207(01)00610-4|
|Appare nelle tipologie:||1.1 Articolo in rivista|