Protective action by hemin against interleukin-1β induced inhibition of rat pancreatic islet function
1994; Elsevier BV; Volume: 103; Issue: 1-2 Linguagem: Inglês
10.1016/0303-7207(94)90076-0
ISSN1872-8057
Autores Tópico(s)Adipose Tissue and Metabolism
ResumoWe have presently investigated the putative protective role of hemin against the inhibitory actions of the cytokine interleukin-1β (IL-1β) on isolated rat pancreatic islets. For this purpose, islets were isolated from adult rats, pre-cultured for 3–7 days in RPMI 1640 medium + 10% fetal calf serum and then exposed to IL-1β (5 ng/ml), hemin for 1, 7 or 24 h after which islet nitrite production, aconitase activity, glucose oxidation rates, glucose-stimulated insulin release and medium insulin accumulation were determined. It was found that hemin did not prevent IL- 1β induced nitrite production. On the other hand, hemin partially counteracted the IL-1β induced decrease in aconitase activity, glucose oxidation, insulin release and medium insulin accumulation. This protective effect was present at a hemin concentration of 10μM and most pronounced at 100μM. Furthermore, hemin induced the synthesis of a 31 kDa protein, which was shown to be heme oxygenase as demonstrated by Western blot analysis. Finally, the protease inhibitor N-α-p-tosyl-l-lysine chloromethyl ketone (TLCK), which protects against IL- 1β by decreasing nitric oxide production, was found to act additively in combination with hemin in alleviating the IL-1β effects. It is proposed that the beneficial effects of hemin against IL-1β could be related to scavenging of nitric oxide and/or an increased resistance to nitric oxide production
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