TXNIP公司
胰岛素抵抗
硫氧还蛋白相互作用蛋白
胰岛素受体
胰岛素
邻苯二甲酸盐
蛋白激酶B
PI3K/AKT/mTOR通路
过剩4
内分泌学
内科学
药理学
氧化应激
生物
化学
医学
信号转导
硫氧还蛋白
生物化学
有机化学
作者
Wang Zhang,Peng Xu,Jing-Ya Li
标识
DOI:10.1016/j.fct.2022.113045
摘要
The widespread usage of plastic products in human life has led to extensive exposure to plasticizers and resulted in serious health problems for humans, which has become a focus of toxicology research in the world. We aimed to explore the potential mechanism of liver insulin resistance induced by di(2-ethylhexyl) phthalate (DEHP) and working on a novel treatment to alleviate insulin resistance caused by excessive exposure to DEHP. For this purpose, in vivo and in vitro experiments were conducted, and the pivotal factors in the insulin signaling pathway were analyzed. In vivo study showed DEHP could lead to liver injury and insulin resistance. DEHP could break the balance of oxidative stress and cause accumulation of inflammatory factors. Genomics and proteomics experiment results revealed that DEHP could inhibit the mRNA and protein expression of insulin receptor, insulin receptor substrate, PI3K/Akt/mTOR, and glucose transporter 4. Nevertheless, the liver insulin resistance induced by DEHP could be reversed by Verapamil (thioredoxin interacting protein (TXNIP) inhibitor). Thus, we confirmed that DEHP caused insulin resistance by affecting the TXNIP in liver, further damaging the conduction of insulin signaling pathway. Therefore, adding Verapamil to the treatment of patients with insulin resistance due to plasticizers might be more effective.
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