Cyanidin 3-glucoside protects 3T3-L1 adipocytes against H2O2- or TNF-α-induced insulin resistance by inhibiting c-Jun NH2-terminal kinase activation
Cyanidin 3-glucoside protects 3T3-L1 adipocytes against H2O2- or TNF-α-induced insulin resistance by inhibiting c-Jun NH2-terminal kinase activation
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DOI：
10.1016/j.bcp.2007.11.016
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发表时间：
2008-03-15
影响因子：
5.8
通讯作者：
Xia, Min
中科院分区：
文献类型：
--
作者：
Guo, Honghui;Ling, Wenhua;Xia, Min
花青素是一种天然存在的植物色素，具有一系列的药理作用。我们先前的研究表明，富含花青素的黑米色素提取物可以预防和改善高果糖诱导的大鼠胰岛素抵抗。本研究以黑米中含量最高的一种典型花青素--花青素-3-葡萄糖苷(Cy-3-G)为研究对象，研究了其对过氧化氢(葡萄糖氧化酶产生)或肿瘤坏死因子-α(TNF-α)对3T3-L1脂肪细胞胰岛素敏感性的保护作用。3T3-L1脂肪细胞暴露于H_2O_2或肿瘤坏死因子-α12h后，c-jun氨基末端激酶(JNK)活性和胰岛素受体底物1(IRS1)丝氨酸307的磷酸化增加，同时胰岛素刺激的IRS1酪氨酸磷酸化和细胞葡萄糖摄取减少。通过RNA干扰阻断JNK的表达，有效地阻止了过氧化氢或肿瘤坏死因子-α诱导的胰岛素作用缺陷。Cy-3-G可降低细胞内活性氧的产生和JNK的激活，并以剂量依赖的方式减轻H_2O_2或TNF-α诱导的胰岛素抵抗。同时，抗氧化剂N-乙酰半胱氨酸没有表现出对肿瘤坏死因子-α诱导的胰岛素抵抗的减弱作用。综上所述，这些结果表明Cy-3-G通过抑制JNK信号通路对H_2O_2或TNF-α诱导的3T3-L1脂肪细胞的胰岛素抵抗起到保护作用。(C)2007 Elsevier Inc.保留所有权利。
Anthocyanins are naturally occurring plant pigments and exhibit an array of pharmacological properties. Our previous study showed that black rice pigment extract rich in anthocyanin prevents and ameliorates high - fructose -induced insulin resistance in rats. In present study, cyanidin 3-glucoside (Cy-3-G), a typical anthocyanin most abundant in black rice was used to examine its protective effect on insulin sensitivity in 3T3-L1 adipocytes exposed to H2O2 (generated by adding glucose oxidase to the medium) or tumor necrosis factor alpha (TNF-alpha). Twelve-hour exposure of 3T3-L1 adipocytes to H2O2 or TNF-alpha resulted in the increase of c-Jun NH2-terminal kinase (JNK) activation and insulin receptor substrate 1 (IRS1) serine 307 phosphorylation, concomitantly with the decrease in insulin-stimulated IRS1 tyrosine phosphorylation and cellular glucose uptake. Blocking JNK expression using RNA interference efficiently prevented the H2O2- or TNF-alpha-induced defects in insulin action. Pretreatment of cells with Cy-3-G reduced the intracellular production of reactive oxygen species, the activation of JNK, and attenuated H2O2- or TNF-alpha-induced insulin resistance in a dose-dependent manner. In parallel, N-acetyl-cysteine, an antioxidant compound, did not exhibit an attenuation of TNF-alpha-induced insulin resistance. Taken together, these results indicated that Cy-3-G exerts a protective role against H2O2- or TNF-alpha-induced insulin resistance in 3T3-L1 adipocytes by inhibiting the JNK signal pathway. (c) 2007 Elsevier Inc. All rights reserved.