This novel finding is approved by the following evidences: 1) APL treatment notably time- and dose-dependently enhanced glucose uptake capability and up-regulated of p-IRS-1 and p-Akt proteins in palmitate -induced insulin resistance of L6 skeletal muscle myotubes; 2) AMPK activation resulted in APL-induced insulin resistance improvement; 3) FGF21 was involved in APL–induced AMPK activation; and 4) APL was a potential PPARγ agonist, and PPARγ activation was required for APL-induced FGF21- AMPK signaling pathway. The gene discussed is IRS1; the disease is acute promyelocytic leukemia.