Regulation of Serine/Threonine Kinases in Skeletal Muscle

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DESCRIPTION (provided by applicant): Exercise has beneficial effects on the treatment as well as prevention of type 2 diabetes. Physical activity activates diverse metabolic signaling pathways in skeletal muscle, and over time induces modification of metabolic gene expression. A novel protein, sucrose-non-fermenting protein kinase 1 /AMPK-related kinase (SNARK), has been identified as a putative signaling protein in skeletal muscle and has been hypothesized to regulate multiple metabolic functions. Studies have shown that SNARK is expressed in skeletal muscle and it was found that exercise and contraction increase SNARK activity in both rodent and human skeletal muscle. The overall goal of the proposed research project is to elucidate the regulation and function of SNARK in mediating the effects of exercise in skeletal muscle. For this purpose, four specific aims were identified: 1) To elucidate the mechanism of SNARK activation in skeletal muscle; 2) To determine whether SNARK mediates fatty acid metabolism in skeletal muscle; 3) To determine the role of SNARK signaling in exercise training- induced adaptations in skeletal muscle; and 4) To determine the function of skeletal muscle SNARK in whole body metabolism. Elucidating the function of SNARK will be important in understanding exercise-stimulated metabolic adaptations and has the potential to define new pharmacological targets for both treatment and prevention of type 2 diabetes. PUBLIC HEALTH RELEVANCE: Diabetes is a major public health concern and exercise has an undisputed role in the treatment and prevention of this disease. The goal of this research proposal is to determine the role of the novel AMPK-related kinase SNARK in regulating metabolic responses to exercise in skeletal muscle. This will lead to a better understanding of the beneficial effects of exercise in diabetes and could help to identify novel therapies for diabetes.