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.