title: A protective role for heme oxygenase expression in pancreatic islets exposed to interleukin-1beta.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, the State University of New York, Buffalo 14214, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ye
authors.forename: S G
authors.initials: SG
authors.lastname: Laychock
mesh_terms: D000818:Animals; D003035:Cobalt / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D006427:Hemin / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007375:Interleukin-1 / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D009573:Nitrites / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats
chemical_list: D007328:Insulin; D007375:Interleukin-1; D009573:Nitrites; D011524:Protoporphyrins; D009569:Nitric Oxide; D003035:Cobalt; D006427:Hemin; D006419:Heme Oxygenase (Decyclizing); D005947:Glucose