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胰岛素受体底物的功能及其基因多态性与2型糖尿病的关系

         

摘要

OBJECTIVE: To investigate the relationship of the function and gene polymorphism of insulin receptor substrate (IRS) with type 2 diabetes mellitus (T2DM), and to provide a new perspective for T2DM drug development. METHODS: Relevant literatures included in CNKI, Wanfang, VIP, PubMed, SpringerLink and other databases from Jan. 1991 to Nov. 2017 were retrieved by using "Insulin receptor substrate" "Type 2 diabetes" "Insulin resistance" "Polymorphism" as Chinese keywords, and "Insulin receptor substrate" "IRS" "Type 2 diabetes" "Insulin resistance" "Polymorphism" as English keywords. The relationship of the function and gene polymorphism of IRS family with T2DM was reviewed. RESULTS & CONCLUSIONS: A total of 328 literatures were retrieved, of which there were 38 valid literatures. At present, IRS family has six members (IRS-1 to IRS-6). The dysfunction of IRS-1 and IRS-2 will lead to insulin resistance and induce T2DM. The relationship of IRS-3 and IRS-4 with T2DM remains controversial. IRS-5 and IRS-6 were newly found and their functions are not clear. The Gly972Arg mutation of IRS-1 is positively correlated with the pathogenesis of T2DM. Gly1057Asp mutation of IRS-2 combined with obesity can induce insulin resistance, but there is controversy. The mutation types of IRS family other members include Ala94Thr, Ala512Pro and Ser892Gly mutation of IRS-1, ACC, Ala157Thr and Leu647Val mutation of IRS-2. The relationship between these types of mutation and T2DM has not yet been fully supported. Multiracial and large-scale studies are required. Some achievements have been made in the present study, but the study is not yet comprehensive. Relationship of IRS family members and their mutation sites with T2DM still needs to be further tested in the expanded population.%目的:了解胰岛素受体底物(IRS)的功能及其基因多态性与2型糖尿病的关系,为2型糖尿病的药物开发提供新的视角和思路.方法:以"胰岛素受体底物""2型糖尿病""胰岛素抵抗""基因多态性"为中文关键词,以"Insulin receptor substrate" "IRS""Type2 diabetes""Insulin resistance""Polymorphism"为英文关键词,组合查询1991年1月-2017年11月在中国知网、万方、维普、 PubMed、SpringerLink等数据库中的相关文献,对IRS家族的功能、基因多态性与2型糖尿病之间的关系进行综述.结果与结论:共检索到相关文献328篇,其中有效文献38篇.目前,已发现的IRS家族成员有6个(IRS-1~IRS-6).IRS-1和IRS-2功能异常会导致胰岛素抵抗、诱发2型糖尿病;IRS-3和IRS-4与2型糖尿病的相关性尚不明确;IRS-5和IRS-6发现最晚,其蛋白功能尚不明确.IRS-1常见的Gly972Arg突变与2型糖尿病的发病呈正相关性;IRS-2的Gly1057Asp突变联合肥胖会诱导胰岛素抵抗,但该结论尚存在争议;IRS家族其他突变类型,包括IRS-1的Ala94Thr、Ala512Pro和Ser892Gly突变,IRS-2的ACC、Ala157Thr和 Leu647Val突变等,这些突变类型与2型糖尿病的关系尚无充分论据支撑,还需要开展多人种、大样本量的研究.尽管目前的研究已经取得了一些进展,但研究尚不全面,IRS家族各成员及其突变位点与2型糖尿病的相关性仍需要在扩大的人群中进行进一步的验证试验.

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