A protective role for heme oxygenase expression in pancreatic islets exposed to interleukin-1beta

Endocrinology. 1998 Oct;139(10):4155-63. doi: 10.1210/endo.139.10.6244.


Heme oxygenase (HO)-1 expression was investigated in rat isolated pancreatic islets. Freshly isolated islets showed no evidence of HO-1 expression. After a 20-h culture, there was a small increase in HO-1 in control islets, and interleukin-1beta (IL-1beta) induced HO-1 expression above control levels. N(G)-monomethyl-L-arginine inhibited the IL-1beta-induced increase in HO-1. Sodium nitroprusside-generated nitric oxide also increased HO-1 expression. CoCl2 induced a concentration- and time-dependent increase in HO-1, but not heat shock protein 70, expression. Cobalt chloride (CoCl2) protected islets from the inhibitory effects of IL-1beta on glucose-stimulated insulin release and glucose oxidation. Nickel chloride did not mimic the effects of CoCl2. An inhibitor of HO-1 activity, zinc-protoporphyrin IX (ZnPP), prevented the protective effect of CoCl2 on insulin release with IL-1beta but did not affect HO-1 expression or the inhibitory response to IL-1beta alone. ZnPP also inhibited the protective effect of hemin in IL-1beta-treated islets. CoCl2 inhibited the marked increase in islet nitrite production in response to IL-1beta. Cobalt-protoporphyrin IX (CoPP), which increased HO expression and activity, also protected islets from the inhibitory effects of IL-1beta, even though IL-1beta largely blocked the CoPP-induced increase in HO-1 expression. In betaHC9 cells, CoCl2 increased HO-1 expression and HO activity, whereas CoPP directly activated HO. ZnPP inhibited basal and CoCl2-stimulated HO activity. Thus, increased HO-1 expression and/or HO activity in response to CoCl2, CoPP, and hemin, seems to mediate protective responses of pancreatic islets against IL-1beta. HO-1 may be protective of beta-cells because of the scavenging of free heme, the antioxidant effects of the end-product bilirubin, or the generation of carbon monoxide, which might have insulin secretion-promoting effects and inhibitory effects on nitric oxide synthase.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cobalt / pharmacology
  • Glucose / metabolism
  • Heme Oxygenase (Decyclizing) / physiology*
  • Hemin / pharmacology
  • Insulin / metabolism
  • Insulin Secretion
  • Interleukin-1 / pharmacology*
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / enzymology
  • Male
  • Nitric Oxide / biosynthesis
  • Nitrites / metabolism
  • Protoporphyrins / pharmacology
  • Rats


  • Insulin
  • Interleukin-1
  • Nitrites
  • Protoporphyrins
  • Nitric Oxide
  • Cobalt
  • Hemin
  • Heme Oxygenase (Decyclizing)
  • Glucose