We found that the body weight, blood glucose, insulin resistance and erectile function of the treated mice were significantly decreased, and the expression of contractile phenotypic marker α-SMA was increased, while the synthetic phenotypic marker OPN was decreased, the corpus cavernosum smooth muscle fibers were increased, and PI3K/AKT/mTOR signaling pathway was activated.We established an in vitro model of spongy smooth muscle cultured with high oleic acid and high glucose and treated it with Nesfatin 1. Here, SPP1 is linked to Insulin resistance.