The inducible form of nitric oxide synthase (iNOS) in insulin-producing cells

The enzyme nitric oxide synthase catalyzes the conversion of L-arginine to citrulline and the radical nitric oxide, a short-lived mediator which can be produced in a variety of cell types. Overproduction of nitric oxide is probably implicated in the pathogenesis of several immunologically mediated diseases, including insulin-dependent diabetes mellitus (Type 1). Insulin-producing cells exposed to cytokines, especially interleukin-1, express an inducible form of nitric oxide synthase which is similar to that observed in activated macrophages. Induction of this enzyme mRNA in these cells depends on protein synthesis, and it is probably modulated by protein products of early response genes, such as C-fos. Cytokines seem to activate beta-cell inducible-nitric oxide synthase mostly by stimulating mRNA transcription, but drugs such as nicotinamide and dexamethasone inhibit interleukin 1 induced nitric oxide production by posttranscriptional mechanisms. Considering the potential role for nitric oxide in beta-cell damage during the early stages of Type 1 diabetes, it is of high relevance to further characterize the regulation of this enzyme in insulin-producing cells.