INS and endothelial dysfunction: High fasting insulin levels and hyperinsulinemia, respectively, may promote atherogenesis by inducing endothelial dysfunction (by reducing the activation of endothelial NO synthase) (14), pro-inflammatory activity of macrophages (15), suppression of autophagy and an increase in protein synthesis (e.g., by upregulating the mechanistic target of rapamycin complex 1) (16), as well as a compromised cytoprotective response to oxidative and other chemical stress (by suppressing the nuclear factor Nrf2) (17).