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

Abstract

The deleterious effects of interleukin 1 (IL-1) on insulin-producing β-cells are partly mediated by the generation of the free radical nitric oxide (NO). We aimed to assess the effect of several steroidal hormones on IL-1β-induced inhibition of rat islet insulin secretion in vitro, and their possible regulatory effects on NO production. Incubation of newborn rat islets for 24 h in the presence of 150 pg/ml IL-1β revealed that dexamethasone dose-dependently attenuated the inhibitory effect of IL-1β on insulin release in response to a 2-h glucose challenge. Physiological and supraphysiological concentrations of testosterone, 17β-estradiol, progesterone, 1,25-dihydroxyvitamin-D3and vitamin D analogues (KH1060 and MC1288) were ineffective. Dexamethasone (1 μM) increased the production of NO in IL-1β-treated rat islets, as measured by the concentration of nitrite in the media. However, 1–5 μM dexamethasone inhibited IL-1β-induced NO production by RIN cells. Dexamethasone (1 μM) did not affect the inhibitory action of the NO donor S-nitroso penicillamine (500 μM) on rat islet insulin secretion. We conclude that dexamethasone partially protects against IL-1β-induced inhibition of rat islet insulin secretion, an effect which is not mediated through modulation of the NO pathway.