Intriguingly, Os-pep, as an adiponectin-mimetic nonapeptide, had beneficial effects by activating AdipoR1/AMPK signaling to prevent neuronal insulin resistance by reducing p-IRS-1Ser636/312 levels and stimulating the p-IRS-1Tyr632 and p-PI3K/Akt/GSK3βSer9 pathways through an AdipoR1/AMPK-dependent mechanism. This evidence concerns the gene ADIPOR1 and Insulin resistance.