Figure 1.

Renin-angiotensin-aldosterone system and regulation of insulin signaling phosphorylation of docking protein insulin receptor substrate -1 (IRS-1) is the major converging point in insulin signaling. The phosphorylation of serine residues of IRS-1 by mammalian target of ribosomal p70 S6 kinase (S6K1) acts as a convergence point for the regulation of IRS-1 phosphorylation by nutrients, hormones, and cytokines. Activation of RAAS in endothelial cells and vascular smooth muscle cells leads to inhibition of insulin signaling though phosphorylation of serine residues of IRS-1. This results in impaired signaling though attenuation of phosphatidylinsositol-3 kinase (PI3- kinase)/protein kinase B (Akt) signaling pathway linked to metabolic insulin signaling. This leads to reduced production of nitric oxide and endothelial dysfunction and altered vascular smooth muscle function.