Journal of Clinical Endocrinology & Metabolism, Vol 76, 399-403, Copyright © 1993 by Endocrine Society

ARTICLES

Predominance of stimulatory effects of interleukin-1 beta on isolated human pancreatic islets

DL Eizirik, N Welsh and C Hellerstrom
Department of Medical Cell Biology, Uppsala University, Sweden.

The aim of the present study was to characterize the effects of human recombinant interleukin-1 beta (rIL-1 beta) on human pancreatic islets. For this purpose, islets isolated from adult cadaveric donors were exposed to rIL-1 beta (1 or 3 ng/mL) for different periods of time. In some experiments, rat pancreatic islets were exposed in parallel to the cytokine. After 48 h of culture in the presence of rIL-1 beta, the human islets showed an increased insulin release during short term incubations in the presence of 1.7 or 16.7 mM glucose. There was also a 3- to 4-fold increase in insulin accumulation into the culture medium, but rIL-1 beta did not affect human islet glucose metabolism. These stimulatory effects of rIL-1 beta on human islets were already present after an acute (2-h) exposure to the cytokine, and this functional stimulation was blocked by an IL-1 receptor antagonist protein. After exposure of human islets to rIL-1 beta for 6 days, there was no effect of the cytokine on either glucose metabolism or insulin release compared to those in control islets. Rat islets exposed for 48 h in culture to the same concentrations of rIL-1 beta, however, showed a 40- 60% decrease in insulin accumulation into the medium, glucose-induced insulin release, and glucose oxidation. Moreover, while there was no effect of rIL-1 beta on nitrite production by human islets, there was a 7- to 11-fold increase in nitrite production by rat islets. Nitrite is an end product of the highly reactive radical nitric oxide (NO), and there are data to suggest that NO is an important mediator of the suppressive and cytotoxic actions of IL-1 on rat islets. The present observations suggest that human islets are less sensitive to the inhibitory effects of human rIL-1 beta than rat islets, and that this is due to a lack of induction of NO synthesis by the cytokine in human islet cells.

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