Curcumin attenuates the effects of insulin on stimulating hepatic stellate cell activation by interrupting insulin signaling and attenuating oxidative stress.
Curcumin attenuates the effects of insulin on stimulating hepatic stellate cell activation by interrupting insulin signaling and attenuating oxidative stress.
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姜黄素通过中断胰岛素信号传导和减弱氧化应激来减弱胰岛素刺激肝星状细胞活化的作用
DOI：
10.1038/labinvest.2009.115
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发表时间：
2009-12
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
作者：
与II型糖尿病（T2 DM）相关的高胰岛素血症是非酒精性脂肪性肝炎（NASH）和肝纤维化的风险因素。肝星状细胞（HSC）是肝纤维化过程中胶原合成的主要效应细胞。升高的胰岛素水平刺激HSC活化。除了抗糖尿病作用外，抗氧化剂姜黄素（咖喱中的黄色色素）还能抑制HSC活化，并在体外和体内保护肝脏免受纤维化。本研究旨在评价姜黄素对胰岛素诱导的HSC活化的影响，并进一步阐明其机制。我们报道姜黄素剂量依赖性地通过抑制I型胶原基因和其他与HSC活化相关的关键基因的表达来消除胰岛素诱导的HSC活化。另外的实验表明，姜黄素通过降低胰岛素受体（InsR）的磷酸化水平和抑制InsR的基因表达来中断HSC中的胰岛素信号传导。此外，姜黄素通过诱导谷氨酸-半胱氨酸连接酶（GCL）的基因表达，导致谷胱甘肽的从头合成和InsR基因表达的抑制，从而减弱胰岛素诱导的HSC中的氧化应激。这些结果支持了我们最初的假设，即姜黄素通过阻断胰岛素信号传导和减弱氧化应激来抑制胰岛素对刺激HSC活化的作用。我们的研究结果提供了新的见解姜黄素抑制胰岛素诱导的HSC激活的机制。
Hyperinsulinemia associated with type II diabetes mellitus (T2DM) is a risk factor for non-alcoholic steatohepatitis (NASH) and hepatic fibrosis. Hepatic stellate cells (HSCs) are the major effectors in collagen production during hepatic fibrogenesis. Elevated levels of insulin stimulate HSC activation. In addition to its anti-diabetic effects, the antioxidant curcumin, the yellow pigment in curry from turmeric, suppresses HSC activation and protects the liver from fibrogenesis in vitro and in vivo. This study aims at evaluating the effect of curcumin on insulin-induced HSC activation and further elucidating the underlying mechanisms. We report that curcumin dose-dependently eliminates insulin-induced HSC activation by suppressing expression of type I collagen gene and other key genes relevant to HSC activation. Additional experiments indicate that curcumin interrupts insulin signaling in HSCs by reducing the phosphorylation level of insulin receptor (InsR) and suppressing gene expression of InsR. Furthermore, curcumin attenuates insulin-induced oxidative stress in HSCs by inducing gene expression of glutamate-cysteine ligase (GCL), leading to de novo synthesis of glutathione and the suppression of gene expression of InsR. These results support our initial hypothesis that curcumin inhibits the effects of insulin on stimulating HSC activation by interrupting insulin signaling and attenuating oxidative stress. Our results provide novel insights into the mechanisms by which curcumin inhibits the insulin-induced HSC activation.
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DOI：
10.1111/j.1440-1746.2007.05277.x
发表时间：
2008-03-01
影响因子：
4.1
作者：
De Minicis, Samele;Brenner, David A.
通讯作者：
Brenner, David A.
影响因子：
2.9
作者：
Murugan, Pidaran;Pari, Leelavinothan;Rao, Chippada Appa
通讯作者：
Rao, Chippada Appa
影响因子：
4.8
作者：
Chen, AP;Zhang, L
通讯作者：
Zhang, L
影响因子：
29.4
作者：
Khamzina, L;Gruppuso, PA;Wands, JR
通讯作者：
Wands, JR
影响因子：
5
作者：
Lin, Jianguo;Chen, Anping
通讯作者：
Chen, Anping