Targeted overexpression of Cu/Zn superoxide dismutase protects pancreatic beta-cells against oxidative stress.
Current evidence suggests that reactive oxygen species (ROS) may participate in the destruction of pancreatic beta-cells leading to type 1 diabetes. Genetic factors pre-disposing individual susceptibility to type 1 diabetes might therefore include those affecting the efficacy of ROS metabolism. In a direct in vivo test of this hypothesis, we have generated strains of mice carrying transgenes that supplement basal levels of the radical-scavenging enzyme Cu/Zn superoxide dismutase in the pancreas via directed expression in beta-cells. Expression of these transgenes significantly enhances resistance to alloxan-induced diabetogenesis above that of control animals, thereby providing direct in vivo evidence that genetic variation in ROS metabolism can affect susceptibility to oxidative stress-mediated diabetogenesis.
Kubisch
H M
HM
Department of Nutritional Sciences, University of Guelph, Ontario, Canada.
Wang
J
J
Bray
T M
TM
Phillips
J P
JP
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015139:Blotting, Southern; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics; D005260:Female; D015870:Gene Expression; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013539:Simian virus 40 / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics*
D001786:Blood Glucose; D007328:Insulin; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase