糖尿病脑病与胰岛素抵抗关系的研究进展  

Current progress on diabetic encephalopathy and insulin resistance

作　　者：王中英[1] Xiang Fang Wang Zhongying;Xiang Fang(Department of Internal Medicine,Heze Medical College,Heze 274000,China;University of Texas Medical Branch,Galveston 77555,USA)

机构地区：[1]菏泽医学专科学校内科学教研室,274000 [2]美国德克萨斯大学医学院,加尔维斯顿77555

出　　处：《国际内分泌代谢杂志》2021年第5期463-467,共5页International Journal of Endocrinology and Metabolism

摘　　要：胰岛素抵抗是2型糖尿病的标志,胰岛素信号在大脑功能的建立和维持中发挥重要作用。糖尿病脑病是糖尿病并发症之一,与阿尔茨海默病一样与大脑胰岛素抵抗密切相关。同为异质性失调,两者的核心特征均是胰岛素信号不同节点的异常,涉及胰岛素分子与受体的结合、胰岛素受体的自磷酸化激活、受体底物的活化及胞内信号的转导和调控。而且,二者与蛋白质错误折叠、形成异常构象的淀粉样不溶性聚集物密切相关,其共同的病理表现为Aβ的沉积和Tau蛋白过度磷酸化。越来越多的事实证明,胰岛素原构象的改变、胰岛素受体受损及胰岛淀粉样多肽生成,在糖尿病脑病的发生发展中具有重要作用。蛋白质稳态概念的提出,为2型糖尿病与阿尔茨海默病一样作为一种蛋白质错误折叠病,开启了胰岛素抵抗研究的全新领域。Insulin resistance is the hallmark of type 2 diabetes.Insulin signaling plays an important role in the establishment and maintenance of brain function.As one of the end organ complications of diabetes,diabetic encephalopathy is closely related with insulin resistance in the brain just like Alzheimer's disease.Diabetic encephalopathy and Alzheimer's disease are heterogeneous disorders,and the core characteristics of these disorders are related to abnormal insulin signaling involved in multiple steps such as binding of insulin molecules to receptors,autophosphorylation activation of insulin receptors,activation of insulin receptor substrates,and intracellular signal transduction and regulation.Furthermore,they are closely related to protein misfolding and abnormal amyloid insoluble aggregates.In addition,their common pathological manifestations are deposition of amyloidβ-protein(Aβ)and Tau hyperphosphorylation.There are accumulating evidences show that the alteration of the conformation of proinsulin,the damage of insulin receptor and the production of islet amyloid polypeptide(IAPP)play important roles in occurrence and progression of diabetic encephalopathy.The concept of protein homeostasis,which believes type 2 diabetes is a protein misfolding disease(PMD)like Alzheimer's disease,provides a novel approach for insulin resistance research.

关 键 词：糖尿病脑病 2型糖尿病 胰岛素抵抗 蛋白质错误折叠 

分 类 号：R587.2[医药卫生—内分泌] R747.9[医药卫生—内科学]