AIM:To investigate the effects of Prunus cerasifera Ehrh.polyphenol extract(PCE)on glucose metabolism in insulin-resistant HepG2(IR-HepG2)cells.METHODS:An IR-HepG2 cells model was established using high sugar and high insulin induction;a control group,an insulin resistance(IR)model group,a PCE treatment group with different concentrations,and a metformin treatment group were set up.Cells were treated with 50,100,200,and 400 mg/L of polyphenol extract for 24 hours,respectively,to detect their effects on cellular glucose consumption.At the same time,use thiazole blue(MTT)colorimetry to evaluate cell viability.Real-time PCR and Western blot were used to detect expression of glucose metabolism-related mRNA and proteins.RESULTS:Prunus cerasifera Ehrh.polyphenol ex-tract can significantly increase glucose consumption in IR-HepG2 cells,and cell activity tends to increase and then decline as its concentration increases;At mRNA and protein levels,in addition to significantly increasing the expression of phos-phorylated adenosine monophosphate activated protein kinase(p-AMPK)protein in IR-HepG2 cells,it also decrease gly-cogen synthase kinase 3β(GSK3β)in glycogen synthesis and gluconeogenesis pathways,forked protein O1(FoxO1),peroxisome proliferator activates gamma co-receptor activation 1-alpha(PGC-1α),glucose-6-phosphatase(G6Pase)and phosphoenol pyruvate carboxykinase(PEPCK)expression.CONCLUSION:Prunus cerasifera Ehrh.polyphenol extract can activate the AMPK signaling pathway in IR-HepG2 cells,to further inhibit gluconeogenesis and glycogen synthesis pathways,thereby improving the insulin resistance state of HepG2 cells.