持久性有机污染物致胰岛素抵抗及其潜在病理机制  

Potential Mechanisms of Insulin Resistance Induced by Persistent Organic Pollutants

作　　者：王静[1] 杜宇国[1] 

机构地区：[1]中国科学院生态环境研究中心环境化学与生态毒理学国家重点实验室,北京100085

出　　处：《生态毒理学报》2013年第6期817-823,共7页Asian Journal of Ecotoxicology

基　　金：国家自然科学基金(20890112,21077127);国家重点基础研究发展计划(2009CB421605,2008CB418102)

摘　　要：胰岛素抵抗综合症目前在全世界以惊人的速度增长,成为21世纪公共健康的严重挑战。多例流行病学调查结果已经显示持久性有机污染物与胰岛素抵抗的关联。胰岛素信号传递受损是胰岛素抵抗的本质原因。考察机制发现,可在机体脂肪组织中贮存积累的持久性有机污染物,如二噁英、多氯联苯、溴代阻燃剂、有机氯农药等,可干扰细胞内受体如环芳烃受体、过氧化物酶体增殖物激活受体、导致氧化损伤、线粒体功能障碍并通过慢性炎症介质TNFα的释放及其相关信号调控;进而可能阻扰胰岛素信号传递中关键蛋白InsR或IRS-1/2正常磷酸化,导致胰岛素抵抗。The incidence of insulin reisistance syndrome has increased at a globally alarming rate, being a seri- ous challenge to public health in 21th century. Large scale epidemiological survey has indicated the relation- ship of persistent organic pollutants （POPs） and insulin resistance. Impaired insulin signaling is a common cause of insulin resistance in essential. Investigation has indicated that POPs, such as TCDD （2,3,7,8-tetra- chlorodibenzo-p-dioxin）, PCBs （polychlorinated biphenyls ）, PBDEs （polybrominated diphenyl ethers ） and OCPs （organochlorine pesticides）, accumulated and stored in adipose tissue, could interfere cell signaling of AhR or PPARs receptor, induce oxidative damage and mitochondrial dysfunction, promote TNFa secrection and its related inflammatory cell signaling. After the interference of cellular signal transduction, POPs probably disrupt the normal phosphoration of insulin receptor （InsR） or insulin receptor substrate-1/2 （IRS-1/2） resulting in insulin resistance induction, which may orovide the potential mechanisms of diabetes etiology.

关 键 词：胰岛素抵抗 持久性有机污染物 细胞受体 TNFΑ 信号转导 

分 类 号：X171.5[环境科学与工程—环境科学]