INTERLEUKIN-1-BETA INDUCES NITRIC-OXIDE PRODUCTION AND INHIBITS THE ACTIVITY OF ACONITASE WITHOUT DECREASING GLUCOSE-OXIDATION RATES IN ISOLATED MOUSE PANCREATIC-ISLETS

The aim of this investigation was to further characterize the process of interleukin-lβ (IL-lβ) induced nitric oxide production in isolated pancreatic islets. It was found that both IL-1β and nitroprusside increased islet nitrite production. This effect was paralleled by inhibition of islet aconitase activity and glucose oxidation rates. Neither trifluoroperazinen or aminopterin could prevent the IL-1β induced increase in nitrite production, aconitase inhibition and decrease in glucose oxidation rates. In a second series of experiments, isolated mouse pancreatic islets were exposed to IL-1β for 24 h and subequently used for nitrite production, aconitase activity and glucose oxidation determinations. The islets responded to IL-1β with an increased nitrite production and a decreased activity of aconitase, whereas the islet glucose oxidation rates were not decreased. It is concluded that IL-1β in both rat and mouse islets induces nitric oxide formation and that this induction leads to the inhibition of the Krebs cycle enzyme aconitase. In rat islets this probably leads to an inhibited insulin secretion, whereas IL-1β in mouse islets suppresses insulin secretion by a non-mitochondrial mechanism. © 1992 Academic Press, Inc.