title: Transgenic copper/zinc superoxide dismutase modulates susceptibility to type I diabetes.
abstract: A growing body of evidence suggests that active oxygen is an important participant in the destruction of the pancreatic beta cell, which, in turn, leads to type I or insulin-dependent diabetes mellitus. Consequently, genetic factors predisposing susceptibility to insulin-dependent diabetes mellitus may include those that determine active oxygen metabolism. A direct test of this hypothesis is provided by a transgenic model for increased activity of Cu/Zn superoxide dismutase (EC 1.15.1.1), a principal radical scavenging enzyme. Here we demonstrate that elevated levels of this enzyme provided by a Cu/Zn superoxide dismutase transgene enhance the tolerance of pancreatic beta cells to oxidative stress-induced diabetogenesis. These results show that this transgenic approach holds promise for revealing the role of reactive oxygen in autoimmune models of diabetogenesis as well as in other models of disease pathology in which active oxygen has been implicated.
authors.affiliation: Department of Molecular Biology and Genetics, University of Guelph, ON, Canada.
authors.forename: H M
authors.initials: HM
authors.lastname: Kubisch
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Luche
authors.forename: E
authors.initials: E
authors.lastname: Carlson
authors.forename: T M
authors.initials: TM
authors.lastname: Bray
authors.forename: C J
authors.initials: CJ
authors.lastname: Epstein
authors.forename: J P
authors.initials: JP
authors.lastname: Phillips
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000201:enzymology; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D018384:Oxidative Stress; D010179:Pancreas / Q000201:enzymology; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger; D013482:Superoxide Dismutase