Our long-term goal is to elucidate the physiological function of antioxidant enzymes in human nutrition and health. Our unique experimental models will allow us to reveal the role and mechanism of these enzymes in the cause of diabetes. These data will guide in exploring new potential targets to prevent and treat diabetes.
impact statement issue
Approximately, 10 to 25 percent of the U.S. population suffers from diabetes and insulin or glucose disorders. The reason for the development of this disorder is still unclear.
Selenium, copper, and zinc are essential trace elements for animals and humans; however, in vivo functions of these elements in metabolism and disease are still unclear. Cellular glutathione peroxidase (GPX1) is the first identified and the most abundant selenium-dependent enzyme in mammals. Copper/zinc-superoxide dismutase (SOD1) is considered to be another major cyotosolic antioxidant enzyme.
impact statement response
Using GPX1 and SOD1 single or double knockout mice, we have previously illustrated a dual role of these enzymes. Both protect against oxidative stresses initiated by reactive oxygen species, but appear to promote the stress initiated by reactive nitrogen species. Most intriguingly, we have demonstrated that overexpression of GPX1 induces metabolic syndrome in mice, and hyperinsulinemia is the primary effect of the transgene. Currently, we are using these animal models and their islets to study the molecular mechanism and signal pathway for the regulation of GPX1 and SOD1 in insulin synthesis, secretion, and function. Experimental approaches include microarray, real-time PCR, proteomics, and co-immunoprecipitation for protein and protein interaction. Future development of large-animal models and human clinical investigations are in the planning stages.
impact statement summary
We are applying unique animal models in which important antioxidant enzymes are genetically inactivated. These models will allow us to determine the role of these enzymes in the development of diabetes and the possibility of using them as a metabolic target of treatment.
