氧化应激在2型糖尿病发病机制中的作用研究进展

Progress in the role of oxidative stress in the pathogenesis of type 2 diabetes

氧化应激在2型糖尿病的病理进程中具有重要作用。目前,临床和科研实践中对机体氧化应激水平的检测主要基于对活性氧(reactive oxygen species,ROS)类、活性氮(reactive nitrogen species,RNS)类和机体脂质过氧化物等氧化应激标志物的检测,方法以物理和化学手段相结合为主。氧化应激主要通过两方面机制诱发糖尿病:(1)对胰岛β细胞的正常功能造成损伤,主要表现为破坏线粒体结构,诱导细胞凋亡,激活核转录因子κB(nuclear transcription factorκB,NF-κB)信号通路,引起细胞炎症反应,抑制胰十二指肠同源盒因子1(pancreatic and duodenal homeobox 1,PDX-1)的核质易位,抑制能量代谢,减少胰岛素合成与分泌;(2)氧化应激诱导胰岛素抵抗的发生,其主要通过干扰胰岛素受体(insulin receptor,InsR)和胰岛素受体底物(insulin receptor substrate,IRS)的磷酸化,影响磷脂酰肌醇3-激酶(phosphatidylinositol 3-kinase,PI3K)的活化,抑制葡萄糖转运子4(glucose transporter 4,GLUT4)的转位以及损伤细胞骨架等与胰岛素信号传递有关的生理活动。研究氧化应激在糖尿病发病机制中的作用,不仅有助于揭示糖尿病的发病机制,也将为糖尿病的预防和治疗提供理论依据。

Diabetes mellitus （DM） is characterized by hyperglycemia and disturbances of carbohydrate and fat metabolism resulted from an absolute or relative deficiency of insulin and insulin resistance. Recent studies indicate that oxidative stress may have a central role in the pathogenesis of type 2 diabetes. Currently, the diagnosis of body oxidative stress level mainly depends on the detection of oxidative stress markers including reactive oxygen species （ROS）, reactive nitrogen species （RNS） and lipid peroxide in clinical and experimental studies with methods combining physical and chemical means. The mechanism underlying oxidative stress-induced diabetes mainly may be through two ways. Firstly oxidative stress damages the normal function of islet β cells, through the destruction of mitochondrial structure and inducing apoptosis, activation of nuclear transcription factor kappa B （NF-κB） signaling pathway, causing cell inflammatory response, and reducing insulin synthesis and secretion by inhibiting pancreatic and duodenal homeobox 1 （PDX-1） nuclear cytoplasm translocation as well as inhibiting energy metabolism; Secondly, oxidative stress induces insulin resistance by interfering physiological activities related to insulin signaling including phosphorylation of insulin receptor （InsR） and insulin receptor substrate （IRS）, the activation of phosphatidylinositol 3-kinase （PI3K） and the translocation of glucose transporter 4 （GLUT4）, as well as injuring the cytoskeleton. Studying the role of oxidative stress in the pathogenesis of diabetes not only helps to reveal the pathogenesis of diabetes, but also provides a theoretical basis for the prevention and treatment of diabetes.