Regulation of Glucose Uptake by AS160 in Skeletal Muscle

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DESCRIPTION (provided by applicant): A major pathological feature of type 2 diabetes is skeletal muscle insulin resistance. Contraction of skeletal muscle results in a very large increase in glucose uptake independent of insulin. The complete signal transduction pathways mediating contraction and insulin stimulated glucose uptake in skeletal muscle are not known, nor is it understood if or where these signaling pathways converge. Novel research from the Goodyear laboratory has recently provided evidence that the Akt Substrate of 160 kDa (AS160) regulates both contraction and insulin stimulated glucose transport in skeletal muscle. Therefore, the primary objective of my research project is to determine how AS160 regulates glucose transport in skeletal muscle. Determining how AS160 regulates glucose uptake requires elucidation of the temporal-spatial dynamics of the AS160 protein network in response to both contraction and insulin. This will be accomplished by determining the subcellular localization of AS160, identifying sites on the AS160 molecule that are phosphorylated, and disovering novel AS160 interacting proteins. These studies will provide important mechanistic data that could eventually lead to novel therapies for the treatment of type 2 diabetes.