Berberine acutely activates the glucose transport activity of GLUT1.
Berberine acutely activates the glucose transport activity of GLUT1.
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DOI：
10.1016/j.biochi.2011.04.013
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发表时间：
2011-07
期刊：
影响因子：
3.9
通讯作者：
Louters, Larry L.
中科院分区：
文献类型：
--
作者：
Cok, Alexandra;Plaisier, Christina;Salie, Matthew J.;Oram, Daniel S.;Chenge, Jude;Louters, Larry L.
黄连素在中医中有着悠久的使用历史，最近被证明对治疗糖尿病有疗效。虽然小檗碱的降血糖作用已在动物和细胞系模型中得到明确证明，如3 T3-L1脂肪细胞和L 6肌管细胞，但作用机制似乎很复杂，数据表明胰岛素信号传导途径的激活以及运动或AMP激酶介导的途径的激活。目前还没有关于小檗碱对胰岛素不敏感的葡萄糖转运蛋白GLUT 1转运活性的急性影响的报道。因此，我们研究了小檗碱对L929成纤维细胞（一种仅表达GLUT 1的细胞系）葡萄糖摄取的急性影响。小檗碱激活葡萄糖摄取，在>40 μM时达到最大刺激5倍。在5分钟内测量到显著激活（P<0.05），到30分钟达到最大值。黄连素的效果是不添加剂的最大刺激由其他已知的兴奋剂，叠氮化物，亚甲蓝或葡萄糖剥夺，表明黄连素和这些兴奋剂之间的共享步骤。小檗碱使葡萄糖摄取的Km值从6.7 ± 1.9mM显著降低到0.55 ± 0.08mM，但对葡萄糖摄取的Vmax无影响。AMP激酶抑制剂化合物C不影响小檗碱刺激的葡萄糖摄取，但下游激酶抑制剂部分阻断小檗碱刺激。SB 203580（p38 MAP激酶抑制剂）不影响次最大黄连素激活，但使最大黄连素激活降低26%，而PD 98059（ERK激酶抑制剂）完全阻断次最大黄连素激活，使最大黄连素激活降低55%。从这项研究中可以看出，小檗碱的一部分降血糖作用可以归因于其对GLUT 1转运活性的急性激活。
Berberine, which has a long history of use in Chinese medicine, has recently been shown to have efficacy in the treatment of diabetes. While the hypoglycemic effect of berberine has been clearly documented in animal and cell line models, such as 3T3-L1 adipocytes and L6 myotube cells, the mechanism of action appears complex with data implicating activation of the insulin signaling pathway as well as activation of the exercise or AMP kinase-mediated pathway. There have been no reports of the acute affects of berberine on the transport activity of the insulin-insensitive glucose transporter, GLUT1. Therefore, we examined the acute effects of berberine on glucose uptake in L929 fibroblast cells, a cell line that express only GLUT1. Berberine activated glucose uptake reaching maximum stimulation of five fold at >40 μM. Significant activation (P<0.05) was measured within five minutes reaching a maximum by 30 minutes. The berberine effect was not additive to the maximal stimulation by other known stimulants, azide, methylene blue or glucose deprivation, suggesting shared steps between berberine and these stimulants. Berberine significantly reduced the Km of glucose uptake from 6.7 ± 1.9 mM to 0.55 ± 0.08 mM, but had no effect on the Vmax of uptake. Compound C, an inhibitor of AMP kinase, did not affect berberine-stimulated glucose uptake, but inhibitors of downstream kinases partially blocked berberine stimulation. SB203580 (inhibitor of p38 MAP kinase) did not affect submaximal berberine activation, but did lower maximal berberine stimulation by 26%, while PD98059 (inhibitor of ERK kinase) completely blocked submaximal berberine activation and decreased the maximal stimulation by 55%. It appears from this study that a portion of the hypoglycemic effects of berberine can be attributed to its acute activation of the transport activity of GLUT1.
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