BETA-CELL ANTIOXIDANT TRANSGENES IN DIABETES TRANSPLANT.

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DESCRIPTION: (Adapted from the Investigator's Abstract): Pancreatic beta-cells contain low levels of enzyme systems that protect against reactive oxygen species (ROS). The investigators hypothesize that the deficit in the ability to dispose of ROS is responsible fort the unusual sensitivity of the islet and that increasing protective enzymes will result in resistance to Type 1 and II diabetes and produce more effective transplantation. To test these hypotheses the investigators have produced transgenic mice with increased beta cell levels of catalase, metallothionein and superoxide dismutase. In our initial characterizations the investigators have determined that overexpression of each of these transgenes is benign to beta-cell function. In addition, both catalase and metallothionein provide dramatic protection against streptozotocin induced diabetes. Transgenic islets will be tested for resistance to additional beta cell toxins including hydrogen peroxide, interleukin 1, nitric oxide and superoxide. These transgenic islets will also be tested for improved effectiveness during transplantation experiments into allogenic recipients. Because ROS may be involved in beta cell damage in diabetes, we will test whether transgenic animals are protected from Type 1 and Type II diabetes. These transgenic mice provide an optimal model to test the role of ROS in diabetes.