To further clarify the underlying mechanism that contribute to the attenuated insulin resistance by AMPD1 deficiency in our experimental model, we studied insulin signaling in the present study and demonstrated that AMPD1 deficiency upregulates AMPK/Akt/mTOR/p70 S6 kinase pathway compared to control in skeletal muscle, but not in liver or white adipose tissue, among insulin-sensitive organs under high fat diet feeding. Here, AMPD1 is linked to Insulin resistance.