INS and metabolic disease: Ang II can activate the mitogen-activated protein kinase pathway by stimulating the binding of Grb2 (growth factor receptor-binding protein 2) to insulin receptor subunits and resulted in phosopylation of ERK (extracellular signal-regulated kinases), while it inhibits the PI3K (phosphatidylinositol 3 kinase) pathway by downregulating the phosphorylation of protein kinase B, ultimately interfering with insulin signaling, and aggravating metabolic disorders and insulin resistance [19] which may lead to hyperglycemia and metabolic disorders.