However, previous studies suggest a potential involvement of the MEK pathway in type-2 diabetic mice [43] and the PKA/p-eNOS and AKT/p-eNOS signaling pathways in a mouse model of diet-induced obesity treated with Compound 21, a selective AT2R agonist [54]. This evidence concerns the gene NOS3 and obesity due to melanocortin 4 receptor deficiency.