Studies on the molecular regulation of the inducible form of nitric oxide synthase (iNOS) in insulin-producing cells.

Nitric oxide, a radical generated by the enzyme nitric oxide synthase (iNOS), may be an important mediator of beta-cell damage in early insulin-dependent diabetes mellitus. We have investigated the molecular regulation of iNOS in insulin-producing RINm5F cells. The data obtained suggest that iNOS is maximally induced in these cells by a 6-h exposure to IL-1 beta or TNF-alpha + IFN-gamma, but not by endotoxin. iNOS mRNA degradation is rapid and it is not affected by IL-1 beta. Interestingly, NO seems to induce a negative feedback on iNOS expression, probably by decreasing iNOS transcription.