Experimental validation was conducted using KK-Ay T2DM mice and TNF-α-induced IR in HepG2 cells (IR-HepG2), and we confirmed that mSMG and its representative compound berberine could improve hepatic IR and glycogen synthesis, and its mechanism may be related to the inhibition of TNF-α/JNK1/IRS-2 pathway (Fig. 1). Here, IRS2 is linked to type 2 diabetes mellitus.