In recent decades, numerous pharmaceutical compounds that selectively inhibit the catalytic activities of PDEs have been developed for the treatment of various andrological disorders, and it has also been demonstrated that PDE5i can exert protective effects in different clinical conditions, apart from ED, such as myocardial infarction, endothelial dysfunction, platelet aggregation, insulin resistance and, finally on skeletal muscle functions. Here, INS is linked to endothelial dysfunction.