Combretastatin A-4 activates AMP-activated protein kinase and improves glucose metabolism in db/db mice.
Combretastatin A-4 activates AMP-activated protein kinase and improves glucose metabolism in db/db mice.
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Combretastatin A-4 激活 AMP 激活的蛋白激酶并改善 db/db 小鼠的葡萄糖代谢。
DOI：
10.1016/j.phrs.2008.03.002
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发表时间：
2008-04
影响因子：
9.3
通讯作者：
中科院分区：
文献类型：
--
作者：
据报道，白藜芦醇可增加胰岛素敏感性，同时激活AMP活化蛋白激酶（AMPK），AMPK是能量平衡的关键调节因子，也是2型糖尿病的重要药物靶点。然而，白藜芦醇结构类似物对AMPK活性和胰岛素敏感性的影响在很大程度上仍然未知。在这项研究中，我们分析了几种白藜芦醇结构类似物对HepG 2细胞中AMPK活性的影响，并通过其磷酸化确定考布他汀A-4（CA-4）是AMPK的激活剂。AMPK激活进一步证实了下游乙酰辅酶A羧化酶（ACC）的磷酸化和上游ATP水平的降低。进一步的研究表明，CA-4激活PPAR的转录活性在体外与荧光素酶报告分析。此外，我们发现CA-4激活AMPK，下调肝脏中促凋亡酶mRNA水平，并改善糖尿病db/db小鼠的空腹血糖水平。这些结果表明，白藜芦醇类似物，如CA-4，可以发挥与白藜芦醇相似的功能，并可能提供改善胰岛素敏感性的重要工具。
Resveratrol was reported to increase insulin sensitivity accompanied with the activation of AMP-activated protein kinase (AMPK), which is a key regulator of energy balance and an important drug target for type 2 diabetes. However, the effect of resveratrol structural analogs on AMPK activity and insulin sensitivity is still largely unknown. In this study, we analyzed the effect of several resveratrol structural analogs on AMPK activity in HepG2 cells, and combretastatin A-4 (CA-4) was identified as an activator of AMPK determined by its phosphorylation. AMPK activation was further confirmed by the phosphorylation of downstream acetyl-CoA carboxylase (ACC) and the decrease of upstream ATP level. Further investigation showed that CA-4 activates PPAR transcriptional activity in vitro with the luciferase reporter assay. In addition, we showed that CA-4 activated AMPK and downregulated gluconeogenic enzyme mRNA levels in liver, and improved the fasting blood glucose level in diabetic db/db mice. These results suggested that resveratrol analogs, such as CA-4, can function similarly as resveratrol and may provide important tools for improving insulin sensitivity.
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DOI：
10.1007/978-3-319-77525-8_100075
发表时间：
2018-12
期刊：
Encyclopedia of Big Data Technologies
影响因子：
--
作者：
通讯作者：
--
影响因子：
3
作者：
通讯作者：
--
DOI：
10.1210/jcem.85.1.6229
发表时间：
2000
期刊：
The Journal of clinical endocrinology and metabolism
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1109/icmas.2000.858517
发表时间：
2000-07
期刊：
Proceedings Fourth International Conference on MultiAgent Systems
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.4
作者：
Jones OD;Schall JD;Shen FX
通讯作者：
Shen FX