INSULIN-LIKE-GROWTH-FACTOR-T REVERSES INTERLEUKIN-1-BETA INHIBITION OF INSULIN-SECRETION, INDUCTION OF NITRIC-OXIDE SYNTHASE AND CYTOKINE-MEDIATED APOPTOSIS IN RAT ISLETS OF LANGERHANS

We have previously observed that treatment of rat islets of Langerhans with interleukin-1 beta for 12 h results in nitric oxide-dependent in hibition of insulin secretion, while 48 h treatment increased rates of islet cell death by apoptosis. Here, we demonstrate that interleukin- 1 beta-mediated nitric oxide formation and inhibition of insulin secre tion are significantly reduced by 24 h pretreatment of rat islets of L angerhans with insulin-like growth factor I(IGF-I). IGF-I decreased cy tokine induction of nitric oxide synthase in islets, Use of an arginin e analogue in culture or IGF-T pretreatment of islets mere also effect ive in protecting islets against cytokine-mediated apoptotic cell deat h, We conclude that IGF-I antagonises inhibitory and cytotoxic effects of cytokines in rat islets. (C) 1997 Federation of European Biochemic al Societies.