Role of receptor binding and gene transcription for both the stimulatory and inhibitory effects of interleukin-1 in pancreatic beta-cells.

A brief exposure of pancreatic islets to the cytokine interleukin-1β (IL-lβ) induces an initial stimulatory phase, which is followed by inhibition of islet function and eventually β-cell damage. In the present study we have investigated the effects of IRAP, a blocker of type I IL-1 receptor and actinomycin D, an inhibitor of DNA transcription, on both the stimulatory and inhibitory effects of IL-β on rat pancreatic islets in vitro. The two test agents counteracted the initial stimulatory actions of IL-1β on both islet glucose-induced insulin release and glucose oxidation rates. Furthermore, cycloheximide, an inhibitor of protein synthesis, could also prevent the early IL-l/?-induced stimulation of insulin release. When islets were exposed for 1 hr to IL-1β and studied after 12 hr, there was a 75% inhibition of glucose induced insulin release, a 50% decrease in glucose oxidation rates and a 30% decrease in (pro)insulin biosynthesis. These effects were completely counteracted by coincubation with IRAP or ac...