Curcumin diminishes the impacts of hyperglycemia on the activation of hepatic stellate cells by suppressing membrane translocation and gene expression of glucose transporter-2.
Curcumin diminishes the impacts of hyperglycemia on the activation of hepatic stellate cells by suppressing membrane translocation and gene expression of glucose transporter-2.
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DOI：
10.1016/j.mce.2010.12.028
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发表时间：
2011-02-20
影响因子：
4.1
通讯作者：
Chen, Anping
中科院分区：
文献类型：
--
作者：
Lin, Jianguo;Chen, Anping
关键词：
糖尿病的特点是血糖水平升高，即高血糖，这可能是非酒精性脂肪性肝炎患者肝纤维化的危险因素。肝星状细胞(HSCs)是肝纤维化形成的主要效应细胞。本研究旨在评估高水平葡萄糖对HSC激活的影响，评估植物化学物质姜黄素在减轻葡萄糖影响中的作用，并阐明其可能的机制。在这份报告中，我们测量了细胞内的葡萄糖水平。检测细胞组分中葡萄糖转运蛋白-2(GLUT2)的含量和基因表达。分析细胞谷胱甘肽和氧化应激水平。我们观察到，高水平的葡萄糖诱导了培养的HSC的细胞增殖、I型胶原的产生和与HSC激活相关的基因的表达，并增加了细胞内的葡萄糖水平。姜黄素消除了刺激性影响。姜黄素通过阻断p38MAPK信号通路，阻断GLUT2的膜转位。此外，姜黄素还通过刺激过氧化物酶体增殖物激活受体-γ(PPARγ)活性和谷胱甘肽的从头合成来抑制GLUT2的表达。综上所述，高血糖通过增加细胞内葡萄糖来刺激HSC的激活，而姜黄素通过阻断GLUT2的膜转位和抑制GLUT2的表达来消除这种作用。后者是通过激活PPARγ和减轻氧化应激来实现的。我们的结果为高血糖刺激HSC激活和肝纤维化的影响提供了证据，并为姜黄素消除高血糖引起的HSC激活的机制和治疗糖尿病相关肝纤维化的潜在治疗策略提供了新的见解。
Diabetes is featured by elevated levels of blood glucose, i.e. hyperglycemia, which might be a risk factor for hepatic fibrogenesis in patients with non-alcoholic steatohepatitis. Hepatic stellate cells (HSCs) are the major effectors during hepatic fibrogenesis. This study was designed to evaluate impacts of high levels of glucose on HSC activation, assess roles of the phytochemical curcumin in attenuating the glucose impacts, and elucidate underlying mechanisms. In this report, levels of intracellular glucose were measured. Contents and gene expression of glucose transporter-2 (GLUT2) in cell fractions were examined. Levels of cellular glutathione and oxidative stress were analyzed. We observed that high levels of glucose induced cell proliferation, type I collagen production and expression of genes relevant to HSC activation, and elevated intracellular glucose levels in cultured HSCs. Curcumin eliminated the stimulatory impacts. Curcumin abrogated the membrane translocation of GLUT2 by interrupting the p38 MAPK signaling pathway. In addition, curcumin suppressed glut2 expression by stimulating the activity of peroxisome proliferator-activated receptor-gamma (PPARγ) and de novo synthesis of glutathione. In conclusion, hyperglycemia stimulated HSC activation in vitro by increasing intracellular glucose, which was eliminated by curcumin by blocking the membrane translocation of GLUT2 and suppressing glut2 expression. The latter was mediated by activating PPARγ and attenuating oxidative stress. Our results presented evidence to impacts of hyperglycemia on stimulating HSC activation and hepatic fibrogenesis, and provided novel insights into the mechanisms by which curcumin eliminated the hyperglycemia-caused HSC activation and potential therapeutic strategies for treatment of diabetes-associated hepatic fibrogenesis.
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影响因子：
9.8
作者：
Gholam, Pierre M.;Flancbaum, Louis;Kotler, Donald P.
通讯作者：
Kotler, Donald P.
影响因子：
7.7
作者：
Kim, H;Kim, J;Ahn, Y
通讯作者：
Ahn, Y
DOI：
10.1073/pnas.2536828100
发表时间：
2003-12-23
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
4.8
作者：
Ikonomov, OC;Sbrissa, D;Shisheva, A
通讯作者：
Shisheva, A
影响因子：
5.4
作者：
Kaji, Kosuke;Yoshiji, Hitoshi;Fukui, Hiroshi
通讯作者：
Fukui, Hiroshi