Molecular mechanism of berberine on improving insulin resistance of 3T3-L1 adipocytes induced by high glucose through IKKβ Ser 181 phosphorylation

Objective To study the effect of berberine on insulin resistance of 3T3-L1 adipocytes induced by high glucose and to investigate its possible molecular mechanism.Methods 3T3-L1 Adipocytes were treated with 25 mmol/L glucose with 0.6 nmol/L insulin to induce insulin resistance.Berberine was used for the treatment and Asprin was used for the positive control.2-Deoxy——D-glucose uptaking method was used to observe the transporting rate.Western blotting was used for the determination of IKKβ Ser 181 phosphorylation,IRS-1 Ser 307 phosphorylation,and the protein expression of IKKβ,IRS-1,PI-3K p85,and GLUT4.Results After the treatment with 25 mmol/L glucose with 0.6 nmol/L insulin for 18 h,the insulin-stimulated glucose transportation in 3T3-L1 adipocyte was inhibited by 60%,the protein expression of IRS-1 and PI-3K p85 were reduced;phosphorylation of IKKβ Ser 181 and IRS-1 Ser 307 were induced.Meanwhile,these were reversed by prior treatment of the cells with berberine or Aspirin.But the protein expression of GLUT4 and IKKβ in 3T3-L1 adipocyte was no change during this study.Conclusion The results show that berberine could significantly improve the insulin resistance of 3T3-L1 adipocytes induced by high glucose and its molecular mechanism might be that berberine could decrease the phosphorylation of serine residue of IRS-1 and increase the phosphorylation of tyrosine residue by inhibiting the phosphorylation of IKKβ Ser 181,thereby regulating the protein expression of the signal of insulin to improve the insulin-resistance.