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 inhibitio n of glucose-stimulated insulin secretion. This and other adverse effe cts 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-ce ll line, RINm5F cells. Cells treated with IL-1 beta underwent DNA frag mentation, nuclear condensation, and apoptotic body formation. The pro duction of nitric oxide preceded the appearance of these typical featu res of apoptosis. Inhibition of the nitric oxide synthase activity by N-G-monomethyl-L-arginine prevented IL-1 beta-induced nitric oxide gen eration and apoptotic cell killing. These results show that-besides th e known alterations in beta-cell function-IL-1 beta-induced nitric oxi de production activates the cell death program. 1994 Academic Press, I nc.