Dexamethasone prevents interleukin-1beta-mediated inhibition of rat islet insulin secretion without decreasing nitric oxide production.
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.
Mauricio
D
D
Steno Diabetes Center, Gentofte, Denmark.
Andersen
H U
HU
Larsen
C M
CM
Karlsen
A E
AE
Mandrup-Poulsen
T
T
Nerup
J
J
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D009603:Nitroso Compounds / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011920:Rats, Inbred WF; D013739:Testosterone / Q000494:pharmacology
D000963:Antimetabolites; D007328:Insulin; D007375:Interleukin-1; D009603:Nitroso Compounds; C074279:KH 1060; D009569:Nitric Oxide; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; C024942:S-nitrosopenicillamine; D003907:Dexamethasone; D002117:Calcitriol