Interleukin-1 beta-induced stimulation of insulin release in mouse pancreatic islets is related to diacylglycerol production and protein kinase C activation.

The aim of the present study was to investigate the mechanisms responsible for the acute, stimulatory effects of interleukin-1 beta (rIL-1 beta; 1 ng/ml) on insulin release from mouse pancreatic islets. For this purpose, mouse islets were exposed for 60-120 min to rIL-1 beta and their function and metabolism characterized during this period. The cytokine did not increase insulin release in the presence of 1.7 mM glucose, but both in the presence of 5.6 or 16.7 mM glucose, or 10 mM leucine + 2 mM glutamine, it induced a 60-100% increase in insulin release. Moreover, rIL-1 beta also enhanced the effects of 1 mu/ml glipizide on insulin release, but failed to increase insulin release induced by 30 mM KCl or by glucose plus phorbol ester (TPA; 100 nM). These early stimulatory effects of rIL-1 beta on insulin release were neither accompanied by major increases in glucose or amino acid metabolism, nor by modifications in islet cAMP content, and they were prevented by mannoheptulose, diazoxide or verapamil. rIL-1 beta potentiation of glucose-induced insulin release was not accompanied by modifications in [Ca2+]i, but the cytokine increased diacylglycerol production and induced protein kinase C (PKC) activation. Down-regulation of PKC completely prevented the stimulatory effects of rIL-1 beta on glucose-induced insulin release. In conclusion, rIL-1 beta induces an early stimulation of insulin release in mouse beta-cells by a mechanism independent of glucose metabolism, cAMP generation or modifications in [Ca2+]i. This effect is probably related to diacylglycerol formation and stimulation of PKC.