INS and obesity due to melanocortin 4 receptor deficiency: In vivo, Kubota et al. [12] demonstrated that the expression levels of insulin-stimulated phosphorylations of AKT and eNOS were decreased by 70–80 % in endothelial cells extracted from the abdominal aorta of 8-week high-fat diet-fed mice and ob/ob mice, treated with an insulin concentration of 100 nmol/L for 30 min, indicating that insulin signaling was impaired in the endothelial cells of these obesity models.