We have previously shown that IGF-I increases eNOS phosphorylation in vivo, increases eNOS activity, and leads to nitric oxide dependent relaxation of conduit vessels; therefore, targeting vascular IGF-I resistance may represent a novel therapeutic target to prevent or slow the accelerated vascular disease seen in patients with obesity or T2DM [39]. This evidence concerns the gene IGF1 and obesity due to melanocortin 4 receptor deficiency.