Objective: To investigate the effect of berberine on HepG2 insulin resistance (IR) model and its mechanism. Method: The IR model was established by combining high-glucose (25 mmol·L-1) with high-insulin (1×10-6 mol·L-1) for 24 h. And then

high-dose (1×10-5 mol·L-1) berberine

low-dose (1×10-6 mol·L-1) berberine

and melbine (1×10-3 mol·L-1

positive control) were respectively added in medium and cultured for another 24 h. At last

medium and HepG2 cells were collected. Glucose level was detected by glucose oxidase detection method

and cell reproductive capacity was detected by cell counting kit-8 (CCK-8); pyruvate kinase (PK) was detected by biochemical analyzer; glucokinase (GCK) and glucose transporter 2 (GLUT2) were detected by enzyme linked immunosorbent assay(ELISA) kits. The mRNA expressions of insulin receptor (InsR)

phosphatidylinositol-3-kinase (PI3K)

protein kinase B (Akt)

GLUT2 were detected by Real-time PCR. The proteins expressions of insulin receptor substrate-1 (IRS-1)

PI3K

and p-Akt were detected by Western blot. Result: Compared with normal group

the glucose consumption of the model group was significantly decreased (P<0.01)

and the activities of PK

GCK and GLUT2 were significantly decreased (P<0.01). Compared with model group

Berberine and metformin groups significantly increased cell glucose consumption

and PK

GCK and GLUT2 protein activities notably increased (P<0.01). Compared with normal group

the mRNA expressions of InsR

PI3K

Akt and GLUT2 and the protein expressions of IRS-1

PI3K and Akt were significantly decreased (P<0.01). Compared with model group

berberine and metformin groups significantly increased protein expression of InsR

PI3K

Akt and GLUT2 (P<0.05

P<0.01). Conclusion: Berberine has a noteworthy therapeutic effect on the insulin resistance of HepG2 cells. Its mechanism may be correlated with the promotion of hepatic glucose metabolism by regulating IRS-1/PI3K/Akt signaling pathway.