1. Dexamethasone prevents interleukin-1beta-mediated inhibition of rat islet insulin secretion without decreasing nitric oxide production.
- Author
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Mauricio D, Andersen HU, Larsen CM, Karlsen AE, Mandrup-Poulsen T, and Nerup J
- Subjects
- Animals, Calcitriol analogs & derivatives, Calcitriol pharmacology, Cells, Cultured, Dose-Response Relationship, Drug, Estradiol pharmacology, Insulin Secretion, Interleukin-1 antagonists & inhibitors, Islets of Langerhans cytology, Islets of Langerhans metabolism, Nitroso Compounds pharmacology, Progesterone pharmacology, Rats, Rats, Inbred WF, Testosterone pharmacology, Antimetabolites pharmacology, Dexamethasone pharmacology, Insulin metabolism, Interleukin-1 pharmacology, Islets of Langerhans drug effects, Nitric Oxide biosynthesis
- Abstract
The deleterious effects of interleukin 1 (IL-1) on insulin-producing beta-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-1beta-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-1beta revealed that dexamethasone dose-dependently attenuated the inhibitory effect of IL-1beta on insulin release in response to a 2-h glucose challenge. Physiological and supraphysiological concentrations of testosterone, 17beta-estradiol, progesterone, 1,25-dihydroxyvitamin-D3 and vitamin D analogues (KH1060 and MC1288) were ineffective. Dexamethasone (1 microM) increased the production of NO in IL-1beta-treated rat islets, as measured by the concentration of nitrite in the media. However, 1-5 microM dexamethasone inhibited IL-1beta-induced NO production by RIN cells. Dexamethasone (1 microM) did not affect the inhibitory action of the NO donor S-nitroso penicillamine (500 microM) on rat islet insulin secretion. We conclude that dexamethasone partially protects against IL-1beta-induced inhibition of rat islet insulin secretion, an effect which is not mediated through modulation of the NO pathway.
- Published
- 1997
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