DEXAMETHASONE PREVENTS INTERLEUKIN-1-BETA-MEDIATED INHIBITION OF RAT ISLET INSULIN-SECRETION WITHOUT DECREASING NITRIC-OXIDE PRODUCTION

The deleterious effects of interleukin 1 (IL-1) on insulin-producing b eta-cells are partly mediated by the generation of the free radical ni tric oxide (NO). We aimed to assess the effect of several steroidal ho rmones on IL-1 beta-induced inhibition of rat islet insulin secretion in vitro, and their possible regulatory effects on NO production. Incu bation of newborn rat islets for 24 h in the presence of 150 pg/ml IL- 1 beta revealed that dexamethasone dose-dependently attenuated the inh ibitory effect of IL-1 beta on insulin release in response to a 2-h gl ucose challenge. Physiological and supraphysiological concentrations o f testosterone, 17 beta-estradiol, progesterone, 1,25-dihydroxyvitamin -D-3 and vitamin D analogues (KH1060 and MC1288) were ineffective. Dex amethasone (1 mu M) increased the production of NO in IL-1 beta-treate d rat islets, as measured by the concentration of nitrite in the media . However, 1-5 mu M dexamethasone inhibited IL-1 beta-induced NO produ ction by RIN cells. Dexamethasone (1 mu M) did not affect the inhibito ry action of the NO donor S-nitroso penicillamine (500 mu M) on rat is let insulin secretion. We conclude that dexamethasone partially protec ts against IL-1 beta-induced inhibition of rat islet insulin secretion , an effect which is not mediated through modulation of the NO pathway . (C) 1997 Academic Press Limited.