Protective action by hemin against interleukin-1 beta induced inhibition of rat pancreatic islet function

Mol Cell Endocrinol. 1994 Jul;103(1-2):109-14. doi: 10.1016/0303-7207(94)90076-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitate Hydratase / metabolism
  • Animals
  • Cells, Cultured
  • Drug Interactions
  • Glucose / metabolism
  • Glucose / pharmacology
  • Heme Oxygenase (Decyclizing) / metabolism
  • Hemin / pharmacology*
  • Insulin / metabolism
  • Insulin Secretion
  • Interleukin-1 / pharmacology*
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / physiology*
  • Male
  • Nitrites / metabolism
  • Oxidation-Reduction
  • Rats
  • Rats, Sprague-Dawley
  • Tosyllysine Chloromethyl Ketone / pharmacology


  • Insulin
  • Interleukin-1
  • Nitrites
  • Tosyllysine Chloromethyl Ketone
  • Hemin
  • Heme Oxygenase (Decyclizing)
  • Aconitate Hydratase
  • Glucose