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Research Article

Akt蛋白激酶在代谢-炎症途径交叉对话中的关键作用：HepG2细胞系中的TNF-α下调和胰岛素抵抗的改善。

卷 21, 期 3, 2021

发表于: 27 April, 2020

页: [257 - 264] 页: 8

弟呕挨: 10.2174/1566524020666200427102209

价格: $65

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摘要

背景：血浆游离脂肪酸升高是2型糖尿病的一个主要方面，从病因上讲，在靶细胞中对胰岛素不敏感。 TNF-α对关键胰岛素信号通路元素的抑制作用尚待在胰岛素抵抗性肝细胞中得到证实。因此，在棕榈酸酯诱导的胰岛素抵抗性肝细胞中研究了TNF-α敲低对胰岛素信号转导关键元件的影响。监测Akt丝氨酸激酶（胰岛素信号通路的关键蛋白）的磷酸化作用，以了解TNF-α对胰岛素抵抗可能增强的作用。 方法：采用0.5 mM棕榈酸酯处理和shRNA介导的TNF-α基因敲低，产生胰岛素抵抗性HepG2细胞，并通过ELISA技术确认其下调。蛋白质印迹分析用于评估Akt蛋白的磷酸化状态。 结果：与对照细胞相比，棕榈酸酯诱导的胰岛素抵抗导致TNF-α蛋白过表达分别为8 h，16 h和24 h后的对照细胞高1.2倍，2.78倍和2.25倍。在棕榈酸酯的存在下，与正常细胞相比，TNF-α的表达在TNF-α敲低的细胞中降低了约30％。在TNF-α下调的细胞中，用100 nM胰岛素与0.5 mM棕榈酸酯结合后，Akt磷酸化程度比对照细胞高约62％。 结论：获得的数据表明，TNF-α蛋白表达的降低改善了HepG2细胞中胰岛素刺激的Akt磷酸化，并降低了脂质诱导的糖尿病肝细胞的胰岛素抵抗。

关键词: 胰岛素抵抗，TNF-α，Akt激酶，棕榈酸酯，HepG2细胞，糖尿病。

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