INS and obesity due to melanocortin 4 receptor deficiency: Following the pathophysiological concept that excess intracellular Ca2+ acts as a critical negative regulator of insulin signaling, we screened nine ARBs that are approved by the FDA to treat hypertension and found that azilsartan and candesartan improved insulin signaling by suppressing obesity-associated intracellular Ca2+ overload in the setting of obesity.