Interleukin-1 beta-induced nitric oxide production activates apoptosis in pancreatic RINm5F cells.

Cytokine production during type I insulin-dependent diabetes mellitus has been linked to alterations in beta-cell function such as inhibition of glucose-stimulated insulin secretion. This and other adverse effects of cytokines, including interleukin-1 beta (IL-1 beta) involve the induction of nitric oxide synthase, with production of nitric oxide. Here, we show that IL-1 beta induces apoptosis in a pancreatic beta-cell line, RINm5F cells. Cells treated with IL-1 beta underwent DNA fragmentation, nuclear condensation, and apoptotic body formation. The production of nitric oxide preceded the appearance of these typical features of apoptosis. Inhibition of the nitric oxide synthase activity by NG-monomethyl-L-arginine prevented IL-1 beta-induced nitric oxide generation and apoptotic cell killing. These results show that--besides the known alterations in beta-cell function--IL-1 beta-induced nitric oxide production activates the cell death program.