Protective action by hemin against interleukin-1 beta induced inhibition of rat pancreatic islet function.
We have presently investigated the putative protective role of hemin against the inhibitory actions of the cytokine interleukin-1 beta (IL-1 beta) 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-1 beta (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-1 beta induced nitrite production. On the other hand, hemin partially counteracted the IL-1 beta induced decrease in aconitase activity, glucose oxidation, insulin release and medium insulin accumulation. This protective effect was present at a hemin concentration of 10 microM and most pronounced at 100 microM. 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-alpha-tosyl-L-lysine chloromethyl ketone (TLCK), which protects against IL-1 beta by decreasing nitric oxide production, was found to act additively in combination with hemin in alleviating the IL-1 beta effects. It is proposed that the beneficial effects of hemin against IL-1 beta could be related to scavenging of nitric oxide and/or an increased resistance to nitric oxide production.
Department of Medical Cell Biology, Uppsala University, Sweden.
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Welsh
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Sandler
D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004347:Drug Interactions; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006427:Hemin / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology
D007328:Insulin; D007375:Interleukin-1; D009573:Nitrites; D014107:Tosyllysine Chloromethyl Ketone; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D000154:Aconitate Hydratase; D005947:Glucose