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Accordingly, the overall goal of this project is to define the mechanisms by which insulin resistance and hypertension are induced in these conditions. The first aim will focus on how the ATP-dependent phosphoprotein phosphatase, PP2A, is upregulated in metabolic syndrome, thereby contributing to the reduced insulin sensitivity. To this end, a comprehensive investigation of all aspects of insulin signaling will be conducted, including the insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS) proteins, activation of PI 3-kinase, and association with downstream signaling molecules. We will examine the in vivo and in vitro consequences of insulin resistance on vascular and renal function. The second aim will explore a recently described, novel insulin-like, feedback inhibition of insulin signaling by elevated blood pressure. 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