FIGURE 12.

ANG II signaling in insulin resistance. ANG II negatively regulates the insulin signaling cascade at multiple steps, including IRS-1, PI3K, and Akt, causing insulin resistance. ANG II also inhibits the AMPK signaling cascade, which together with the associated reduction in Sirt3 expression and resultant mitochondrial oxidative stress, contributes to insulin resistance. Furthermore, ANG II indirectly causes insulin resistance via induction of pro-inflammatory cytokines, as well as by suppression of adiponectin secretion.