Andrographolide attenuates tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes

Andrographolide attenuates tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes
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穿心莲内酯可减弱 3T3-L1 脂肪细胞中肿瘤坏死因子 α 诱导的胰岛素抵抗。

DOI:
10.1016/j.mce.2010.10.005
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发表时间:
2011-01-30
影响因子:
4.1
通讯作者:
Zhang, Zhiguo
Zhang, Zhiguo
中科院分区:
医学2区
文献类型:
--
作者:
Jin, Lina;Shi, Guojun;Zhang, Zhiguo

文献摘要

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穿心莲的主要生物活性成分穿心莲内酯(AG)具有抗糖尿病作用。然而,其分子机制尚不清楚。在这项研究中,我们证明AG以时间和剂量依赖的方式增加3T3-L1细胞的葡萄糖摄取。AG对胰岛素信号转导通路的激活始于IRS-1的磷酸化酪氨酸,进而通过磷脂酰肌醇3-激酶(PI3K)及其下游信号转导通路。更重要的是,AG预处理细胞可抑制肿瘤坏死因子-α诱导的核因子-kappaB信号通路的激活及其下游炎症因子的表达,从而改善胰岛素抵抗。综上所述,AG可通过抑制核因子-kappaB途径改善胰岛素敏感性。这些发现有助于理解AG的抗糖尿病特性,并可能对AG在血糖控制中的治疗应用感兴趣。(C)2010爱思唯尔爱尔兰有限公司。保留所有权利。
Andrographolide (AG), the primary bioactive component of Andrographils paniculate Nees, has showed an anti-diabetic effect. However, the molecular mechanism has not been clarified. In this study, we demonstrated that AG increased glucose uptake in 3T3-L1 cells in a time- and dosedependent manner. The activation of insulin signaling by AG was initiated from phosphotyrosine of IRS-1 and further passed on through phosphatidylinositol 3-kinase (PI3K) and the downstream signaling cascades. Moreover importantly, pretreatment cells with AG suppressed the TNF-alpha induced activation of NF-kappa B signaling pathway and its downstream inflammatory factors expression, therefore ameliorating insulin resistance. In conclusion, AG can improve insulin sensitivity through inhibition of NF-kappa B pathway. These findings are helpful in understanding the anti-diabetic properties of AG and can be of interest for the therapeutic application of AG in glucose controlling. (C) 2010 Elsevier Ireland Ltd. All rights reserved.