Insulin-sensitivity in transgenic mice expressing human catalase in mitochondria

• Applicant: Dr. Dirk Thorsten Weismann
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: from 2006 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 33013746

Type 2 diabetes is a rapid growing worldwide pandemic and insulin resistance is the best predictor for the development of type 2 diabetes. Increased amounts of intracellular fatty acids are a common feature in the state of insulin resistance and induce insulin resistance in skeletal muscle by directly inhibiting insulin stimulated glucose transport activity. Impaired insulin stimulated oxidative phosphorylation was shown in insulin resistant subjects and was associated with increased intracellular lipid contents. Thus growing evidence points to mitochondrial dysfunction as a major cause in the development of the metabolic syndrome. In a transgenic mouse model expressing human catalase in mitochondria an increased life span of these animals was demonstrated as a result of preserved mitochondrial function due to reduced detrimental action of hydrogen peroxide. It is planned to determine the role of reactive oxygen species induced mitochondrial damage in the development of insulin resistance by characterizing the glucose metabolism in this transgenic mouse model. This work will contribute to understand the pathophysiology of type 2 diabetes, which is the basis to identify new targets for treatment.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Gerald I. Shulman, Ph.D.