小檗碱抑制IKKβ Ser 181磷酸化改善高糖诱导的3T3-L1脂肪细胞胰岛素抵抗的分子机制  

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

作　　者：易屏[1] 陆付耳[2] 陈广[2] 徐丽君[2] 王开富[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院中医科,湖北武汉430030 [2]华中科技大学同济医学院附属同济医院中西医结合研究所,湖北武汉430030

出　　处：《中草药》2008年第5期724-729,共6页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(30371816)

摘　　要：目的研究小檗碱对高糖诱导的3T3-L1脂肪细胞胰岛素抵抗的作用,探讨小檗碱改善胰岛素抵抗的分子机制。方法以25 mmol/L葡萄糖加0.6 nmol/L胰岛素诱导3T3-L1脂肪细胞产生胰岛素抵抗,予以小檗碱进行干预,同时以阿司匹林作为阳性对照,以2-脱氧-[3H]-D-葡萄糖摄入法观察葡萄糖的转运率,用Western blotting检测IKKβ蛋白,IKKβ Ser 181磷酸化,IRS-1蛋白,IRS-1 Ser 307磷酸化,PI-3K p85蛋白,GLUT4蛋白的表达。结果25 mmol/L葡萄糖加0.6 nmol/L胰岛素作用18 h使3T3-L1脂肪细胞胰岛素刺激的葡萄糖转运抑制60%,IKKβSer 181磷酸化、IRS-1 Ser 307磷酸化的表达增加,IRS-1和PI-3K p85蛋白的表达减少;同时加入小檗碱或阿司匹林则可逆转上述效应。但高糖、小檗碱、阿司匹林对3T3-L1脂肪细胞IKKβ蛋白、GLUT4蛋白的表达无明显影响。结论小檗碱可以明显改善高糖诱导的胰岛素抵抗,其分子机制可能是小檗碱通过抑制IKKβSer181磷酸化,使IRS-1丝氨酸残基磷酸化减少而酪氨酸残基磷酸化增加,调节胰岛素信号蛋白的表达来实现的。Objective To study the effect of berberine on insulin resistance of 3T3-L1 adipocytesinduced 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-[^3H]-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 proteinexpression 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 byprior 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 couldsignificantly 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 andincrease 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.

关 键 词：小檗碱 胰岛素抵抗 IKKΒ 高糖 

分 类 号：R286.72[医药卫生—中药学]