title: Long-lasting expression of HO-1 delays progression of type I diabetes in NOD mice.
abstract: Heme oxygenase-1 (HO-1) is crucial in regulating oxidative injury. The present study was designed to assess whether HO-1 upregulation by cobalt protoporphyrin IX (CoPP) moderates or prevents the diabetic state in non-obese diabetic (NOD) mice, an animal model for Type 1 diabetes (T1D). HO-1 expression and HO activity were upregulated in the pancreas by the intermittent administration of CoPP. This was associated with decreases in blood glucose and pancreatic O2-, but increased pAKT and BcL-XL and cell survival. A considerable number of beta cells were preserved in the islets of CoPP-treated NOD mice, while none were found in untreated diabetic mice. The number of CD11c+ dendritic cells was decreased in the pancreas of CoPP-treated NOD mice (p < 0.05). These novel findings provide a link between the increase in HO-1 and a decrease in infiltrated CD11c+ dendritic cells, and suggest that induction of HO-1 activity can be used to enhance cell survival and moderate the diabetic state in T1D.
authors.affiliation: First Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Stephen
authors.initials: S
authors.lastname: Peterson
authors.forename: Daniel
authors.initials: D
authors.lastname: Husney
authors.forename: Muneo
authors.initials: M
authors.lastname: Inaba
authors.forename: Kequan
authors.initials: K
authors.lastname: Guo
authors.forename: Attallah
authors.initials: A
authors.lastname: Kappas
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
authors.forename: Nader G
authors.initials: NG
authors.lastname: Abraham
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D013995:Time
chemical_list: D001786:Blood Glucose; D051547:Heme Oxygenase-1