Grant: Operating Grant

This CIHR-funded project has focused on the potential role of the mTORC1/S6K1 signaling pathway in the induction of insulin resistance for glucose metabolism in insulin target cells and tissues. We found that IRS-1 Ser phosphorylation by mTORC1 and S6K1 is involved in the development of insulin resistance induced by nutrient satiation and obesity. In the current proposal, we will study the detailed mechanisms by which overnutrition activates the mTORC1/S6K1 pathway in animal models of obesity. We will also determine the potential role of another kinase, RSK, in mediating IRS-1 Ser phosphorylation and inhibition of insulin action on glucose metabolism. These studies will further establish the roles and mechanisms of the mTORC1/S6K1 and RSK pathways in mediated insulin resistance in obesity and upon nutrient satiation, and thus help define novel therapeutic strategies to combat this metabolic syndrome.