In the context of cellular metabolism, three mechanisms by which the RAS, would be altering glucose metabolism and promoting insulin resistance and consequently the development of MetS are described: (a) inhibition of the activation of the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K) pathway; (b) the inhibition of differentiation of preadipocytes, responsible for the production of inflammatory or diabetogenic cytokines; and (c) increase in ROS production, damaging pancreatic B cells and causing endothelial dysfunction (32). Here, IRS1 is linked to endothelial dysfunction.