Berberine stimulates glucose transport through a mechanism distinct from insulin
Berberine stimulates glucose transport through a mechanism distinct from insulin
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DOI：
10.1016/j.metabol.2006.10.025
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发表时间：
2007-03-01
影响因子：
9.8
通讯作者：
Chen, Jialun
中科院分区：
文献类型：
--
作者：
Zhou, Libin;Yang, Ying;Chen, Jialun
黄连素具有降血糖作用，但其机制尚不清楚。在本研究中，小檗碱对葡萄糖摄取的影响，其特征在于在3 T3-L1脂肪细胞。结果表明，黄连素刺激3 T3-L1脂肪细胞的葡萄糖摄取的剂量和时间依赖性的方式，在12小时的最大效果。小檗碱也能增加3 T3-L1前脂肪细胞的葡萄糖摄取。小檗碱刺激的葡萄糖摄取是添加剂的胰岛素在3 T3-L1脂肪细胞，即使在最大有效浓度的两种成分。与胰岛素不同，小檗碱对葡萄糖摄取的影响对磷脂酰肌醇3-激酶抑制剂渥曼青霉素和p38丝裂原活化蛋白激酶抑制剂SB 203580不敏感。小檗碱激活细胞外信号调节激酶（ERK）1/2，但PD 98059，ERK激酶抑制剂，仅减少小檗碱刺激的葡萄糖摄取32%。小檗碱不诱导Akt的Ser 473磷酸化，也不增强胰岛素诱导的Akt磷酸化。小檗碱对葡萄糖转运蛋白4（GLUT 4）的表达和细胞定位无明显影响。小檗碱不增加GLUT 1基因表达。然而，染料木素，酪氨酸激酶抑制剂，完全阻断小檗碱刺激的3 T3-L1脂肪细胞和前脂肪细胞的葡萄糖摄取，表明小檗碱可能通过增加GLUT 1活性诱导葡萄糖转运。此外，小檗碱增加腺苷一磷酸活化蛋白激酶和乙酰辅酶A羧化酶磷酸化。这些研究结果表明，小檗碱增加葡萄糖的摄取，通过一种不同于胰岛素的机制，和激活的腺苷一磷酸激活的蛋白激酶似乎参与了小檗碱的代谢作用。(c)2007爱思唯尔公司All rights reserved.
Berberine exerts a hypoglycemic effect, but the mechanism remains unknown. In the present study, the effect of berberine on glucose uptake was characterized in 3T3-L1 adipocytes. It was revealed that berberine stimulated glucose uptake in 3T3-L1 adipocytes in a dose- and time-dependent manner with the maximal effect at 12 hours. Glucose uptake was increased by berberine in 3T3-L1 preadipocytes as well. Berberine-stimulated glucose uptake was additive to that of insulin in 3T3-L1 adipocytes, even at the maximal effective concentrations of both components. Unlike insulin, the effect of berberine on glucose uptake was insensitive to wortmannin, an inhibitor of phosphatidylinositol 3-kinase, and SB203580, an inhibitor of p38 mitogen-activated protein kinase. Berberine activated extracellular signal-regulated kinase (ERK) 1/2, but PD98059, an ERK kinase inhibitor, only decreased berberine-stimulated glucose uptake by 32%. Berberine did not induce Ser473 phosphorylation of Akt nor enhance insulin-induced phosphorylation of Akt. Meanwhile, the expression and cellular localization of glucose transporter 4 (GLUT4) were not altered by berberine. Berberine did not increase GLUT1 gene expression. However, genistein, a tyrosine kinase inhibitor, completely blocked berberine-stimulated glucose uptake in 3T3-L1 adipocytes and preadipocytes, suggesting that berberine may induce glucose transport via increasing GLUT1 activity. In addition, berberine increased adenosine monophosphate-activated protein kinase and acetyl-coenzyme A carboxylase phosphorylation. These findings suggest that berberine increases glucose uptake through a mechanism distinct from insulin, and activated adenosine monophosphate-activated protein kinase seems to be involved in the metabolic effect of berberine. (c) 2007 Elsevier Inc. All rights reserved.