Aim: To investigate the effects and molecular mechanisms of berberine on improving insulin resistance induced by free fatty acids (FFAs) in 3T3-L1 adipocytes.
Methods: The model of insulin resistance in 3T3-L1 adipocytes was established by adding palmic acid (0.5 mmol/L) to the culture medium. Berberine treatment was performed at the same time. Glucose uptake rate was determined by the 2-deoxy-[(3)H]-D-glucose method. The levels of IkB kinase beta (IKKbeta) Ser(181) phosphorylation, insulin receptor substrate-1(IRS-1) Ser(307) phosphorylation, expression of IKKbeta, IRS-1, nuclear transcription factor kappaB p65 (NF-kappaB p65), phosphatidylinositol-3-kinase p85 (PI-3K p85) and glucose transporter 4 (GLUT4) proteins were detected by Western blotting. The distribution of NF-kappaB p65 proteins inside the adipocytes was observed through confocal laser scanning microscopy (CLSM).
Results: After the intervention of palmic acid for 24 h, the insulin-stimulated glucose transport in 3T3-L1 adipocytes was inhibited by 67%. Meanwhile, the expression of IRS-1 and PI-3K p85 protein was reduced, while the levels of IKKbeta Ser(181) and IRS-1 Ser(307) phosphorylation, and nuclear translocation of NF-kappaB p65 protein were increased. However, the above indexes, which indicated the existence of insulin resistance, were reversed by berberine although the expression of GLUT4, IKKbeta and total NF-kappaB p65 protein were not changed during this study.
Conclusion: Insulin resistance induced by FFAs in 3T3-L1 adipocytes can be improved by berberine. Berberine reversed free-fatty-acid-induced insulin resistance in 3T3-L1 adipocytes through targeting IKKbeta.