title: Overexpression of extracellular-SOD in islets of nonobese diabetic mice and development of diabetes.
abstract: Mice of the nonobese diabetic strain develop a progressive insulitis resulting in beta-cell destruction and diabetes. Superoxide radicals are abundantly formed by leukocytes and other mechanisms in inflammatory reactions. We here aimed to determine whether superoxide radicals contribute to the beta cell destruction in the mouse model. Transgenic nonobese diabetic mice secreting extracellular-superoxide dismutase under control of the insulin promoter were generated and the development of glucosuria monitored. The overexpression of extracellular-superoxide dismutase resulted in a 6-fold increase in the total superoxide dismutase activity of the islets. The incidence of diabetes of the transgenic mice was, however, not modified. The results suggest that superoxide radicals secreted to the extracellular space do not contribute to the beta cell destruction in the nonobese diabetic mouse model.
authors.affiliation: Department of Biomedical Sciences, Clinical Chemistry, Umeå University, Umeå, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Sandström
authors.forename: Lena M
authors.initials: LM
authors.lastname: Jonsson
authors.forename: Helena
authors.initials: H
authors.lastname: Edlund
authors.forename: Dan
authors.initials: D
authors.lastname: Holmberg
authors.forename: Stefan L
authors.initials: SL
authors.lastname: Marklund
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000473:pathology; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006029:Glycosuria / Q000378:metabolism; D015994:Incidence; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
chemical_list: D007328:Insulin; D007527:Isoenzymes; D013481:Superoxides; D013482:Superoxide Dismutase