In a rat model of obesity and type 2 diabetes mellitus, it has been described both a numerical increase and functional abnormalities in intimal VSMC and the occurrence of VSMC accumulation in atherosclerotic lesions, with a direct correlation between VSMC proliferation and insulin concentrations [170, 172, 173]; the involvement of endogenous cytokines (especially TNF-α), and the receptors of advanced glycation end products (AGE) [RAGE] in neointimal formation in obese Zucker rats has been recently recognized [174]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.