Curcumin attenuates BPA-induced insulin resistance in HepG2 cells through suppression of JNK/p38 pathways
Curcumin attenuates BPA-induced insulin resistance in HepG2 cells through suppression of JNK/p38 pathways
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姜黄素通过抑制 JNK/p38 通路减轻 BPA 诱导的 HepG2 细胞胰岛素抵抗
DOI：
10.1016/j.toxlet.2017.03.011
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发表时间：
2017-04-15
影响因子：
3.5
通讯作者：
Zhong, Caiyun
中科院分区：
文献类型：
--
作者：
Geng, Shanshan;Wang, Shijia;Zhong, Caiyun
双酚A（BPA）是一种人工环境内分泌干扰物。越来越多的证据表明，BPA暴露通过多种机制（包括炎症和氧化应激）导致胰岛素抵抗。以前的研究表明姜黄素是一种安全的植物化学物质，可以改善肥胖相关的胰岛素抵抗，炎症和氧化应激。本研究旨在探讨姜黄素在体外对双酚A诱导的胰岛素抵抗的预防作用及其机制。通过BPA处理人肝HepG 2细胞建立体外胰岛素抵抗模型，观察姜黄素的保护作用。我们发现，用100 nM BPA处理HepG 2细胞5天可显著降低葡萄糖消耗，损害胰岛素信号传导，升高促炎细胞因子和氧化应激，并激活信号传导途径;抑制JNK和p38途径，但不抑制ERK和NF-κ B途径，改善BPA处理的HepG 2细胞的葡萄糖消耗和胰岛素信号传导。此外，我们发现，姜黄素有效地衰减BPA触发的胰岛素抵抗的影响范围，而JNK和p38激动剂茴香霉素预处理可以显着补偿姜黄素引起的影响。这些数据说明JNK/p38活化在BPA诱导的胰岛素抵抗中的作用，并建议姜黄素作为干预BPA诱导的胰岛素抵抗的有希望的候选物。(C)2017爱思唯尔B. V.保留所有权利。
Bisphenol A (BPA) is an artificial environmental endocrine disrupting chemicals. Accumulating evidence indicates that exposure to BPA contributes to insulin resistance through diverse mechanism including inflammation and oxidative stress. Previous studies have suggested curcumin as a safe phytochemical which can improve obesity-related insulin resistance, inflammation and oxidative stress. The present study aimed to investigate the ability of curcumin to prevent BPA-induced insulin resistance in vitro and the underlying mechanism. Following the establishmet of in vitro insulin resistance via BPA treatment in human liver HepG2 cells, the protective effects of curcumin were determiend. We showed that treatment of HepG2 cells with 100 nM BPA for 5 days induced significantly decreased glucose consumption, impaired insulin signaling, elevation of pro-inflammatory cytokines and oxidative stress, and activation of signaling pathways; inhibition of JNK and p38 pathways, but not ERK nor NF-kappa B pathways, improved glucose consumption and insulin signaling in BPA-treated HepG2 cells. Moreover, we revealed that curcumin effectively attenuated the spectrum of effects of BPA-triggered insulin resistance, whereas pretreatment with JNK and p38 agonist anisomycin could significantly compensate the effects caused by curcumin. These data illustrated the role of JNK/p38 activation in BPA-induced insulin resistance and suggested curcumin as a promising candidate for the intervention of BPA-induced insulin resistance. (C) 2017 Elsevier B.V. All rights reserved.