IRS1 and endothelial dysfunction: Insulin resistance causes HT via several mechanisms, including enhanced renal sodium absorption, renin angiotensin system (RAS) activation, augmentation of sympathetic nervous system activity, endothelial dysfunction, and increased peripheral and renal vascular resistance.7–13 Nakamura et al. observed a blunting of insulin-mediated glucose uptake in adipose tissue via insulin receptor substrate 1 (IRS1), whereas insulin-mediated sodium reabsorption in the proximal tubule was preserved via insulin receptor substrate 2.