首页> 外文OA文献 >Plasminogen activator inhibitor-1 synthesis in the human hepatoma cell line Hep G2. Metformin inhibits the stimulating effect of insulin.
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Plasminogen activator inhibitor-1 synthesis in the human hepatoma cell line Hep G2. Metformin inhibits the stimulating effect of insulin.

机译:纤溶酶原激活物抑制剂1在人肝癌细胞系Hep G2中的合成。二甲双胍抑制胰岛素的刺激作用。

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摘要

High plasma plasminogen activator inhibitor-1 (PAI-1) activity is associated with insulin resistance and is correlated with hyperinsulinemia. The cellular origin of plasma PAI-1 in insulin resistance is not known. The hepatoma cell line Hep G2 has been shown to synthesize PAI-1 in response to insulin. The aim of this study was to analyze the insulin-mediated response of PAI-1 and lipid synthesis in Hep G2 cells after producing an insulin-resistant state by decreasing insulin receptor numbers. The effect of metformin, a dimethyl-substituted biguanide, known to lower plasma insulin and PAI-1 levels in vivo was concomitantly evaluated. Preincubation by an 18-h exposure of Hep G2 cells to 10(-7) M insulin aimed at reducing the number of insulin receptors, was followed by a subsequent 24-h stimulation with 10(-9) M insulin. The decrease in insulin receptors was accompanied as expected, by a reduction in [14C]acetate incorporation, an index of lipid synthesis, whereas PAI-1 secretion and PAI-1 mRNA expression were enhanced. The addition of metformin did not modify the effect of insulin on insulin receptors or [14C]acetate incorporation. In contrast, the drug (10(-4) M) inhibited insulin-mediated PAI-1 synthesis. The results indicate that PAI-1 synthesis in presence of insulin is markedly increased in down-regulated cells, and that metformin inhibits this effect by acting at the cellular level. These in vitro data are relevant with those found in vivo in insulin-resistant patients. Hep G2 cells may be a suitable model to study PAI-1 regulation in response to hyperinsulinemia.
机译:血浆纤溶酶原激活物抑制剂1(PAI-1)的高活性与胰岛素抵抗相关,并与高胰岛素血症相关。血浆PAI-1在胰岛素抵抗中的细胞起源尚不清楚。肝细胞癌细胞系Hep G2已显示可响应胰岛素而合成PAI-1。这项研究的目的是分析通过减少胰岛素受体数量产生胰岛素抵抗状态后,Hep G2细胞中胰岛素介导的PAI-1反应和脂质合成。同时评估了二甲双胍(一种二甲基取代的双胍)在体内降低血浆胰岛素和PAI-1水平的作用。通过将Hep G2细胞与10(-7)M胰岛素接触18小时进行预孵育,以减少胰岛素受体的数量,随后再进行10(-9)M胰岛素的24小时刺激。胰岛素受体的减少与预期相伴,减少了[14C]乙酸酯的掺入,这是脂质合成的指标,而PAI-1分泌和PAI-1 mRNA表达则得到增强。二甲双胍的添加不会改变胰岛素对胰岛素受体或[14C]乙酸酯掺入的影响。相反,药物(10(-4)M)抑制胰岛素介导的PAI-1合成。结果表明,在存在胰岛素的情况下,PAI-1的合成在下调的细胞中显着增加,二甲双胍通过在细胞水平起作用来抑制这种作用。这些体外数据与在胰岛素抵抗患者体内发现的数据有关。 Hep G2细胞可能是研究对高胰岛素血症作出反应的PAI-1调节的合适模型。

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