肥胖诱导胰岛素抵抗与胰岛素信号通路受损的研究进展  

Research Progress of Obesity-induced Insulin Resistance and Impaired Insulin Signaling Pathway

作　　者：王晨璐 许晨颖 王潇乐 张方方 杨悦 金亮[1] WANG Chen-lu;XU Chen-ying;WANG Xiao-le;ZHANG Fang-fang;YANG Yue;JIN Liang(School of Life Science and Technology,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009

出　　处：《药物生物技术》2022年第6期606-612,共7页Pharmaceutical Biotechnology

基　　金：国家自然科学基金(No.82100858,No.82070801);江苏省青年基金(No.BK20200569)。

摘　　要：糖尿病是当今世界上最常见且普遍的慢性代谢性疾病之一,对于肾脏、心脑血管、神经、眼睛等均有极大的危害性。目前糖尿病主要包括以下四种:1型糖尿病、2型糖尿病、妊娠期糖尿病和特殊类型糖尿病。2017年我国糖尿病患病率持续上升至17.2%,其中2型糖尿病(Type 2 diabetes mellitus, T2DM)比例高达90%以上,因此糖尿病也已成为实施健康中国战略,提升健康水平亟待攻克的难题。肥胖是一种由环境、遗传、饮食、年龄等多种因素相互作用而引起的一种机体代谢紊乱综合征,也是糖尿病发生的重要诱因。T2MD患者和许多肥胖患者都表现出胰岛素刺激的葡萄糖吸收和利用的效率下降,胰岛β细胞出现代偿性增殖并增加总胰岛素的分泌水平从而达到稳定血糖的作用,这一现象被称为胰岛素抵抗(Insulin resistance, IR)。胰岛素是通过其信号通路从而在机体中发挥调控作用,如果整个通路中的某一部分受到损害发生损伤,通路因此无法将上游信息正常传递至下游,胰岛素的调控作用将受到削弱甚至可能消失。当IR发生时,若通路受损,胰岛素无法调控全身葡萄糖稳态。随着IR的发展,当胰腺不能提供过量的胰岛素时,就会导致全身葡萄糖稳态的严重失衡,这将会诱发T2MD以及许多代谢性疾病。近年来已有大量以IR病理机制为主题的研究被报道,文章聚焦于以肥胖及胰岛素信号通路受损为主的IR诱导机制,整理并阐述了相关研究进展,以期为未来的进一步研究提供思路与依据。Diabetes was one of the most common and general chronic diseases in the world, which had great harm to kidney, cardiovascular, nerve and eyes.There are four types of diabetes: Type 1 diabetes, type 2 diabetes, gestational diabetes, and special type diabetes.The prevalence of diabetes continues to increase to 11.2 percent in 2021,with type 2 diabetes mellitus(T2DM) accounting for more than 90 percent.Therefore, diabetes had also become an urgent problem to be solved in implementing the healthy China strategy and improving the health level.Obesity was a metabolic disorder syndrome caused by the interaction of environment, genetics, diet, age and other factors, which was also an important inducement of diabetes.Patients with T2MD and many obese patients show reduced efficiency in insulin-stimulated glucose uptake and utilization, compensatory proliferation of islet β cells and increased levels of total insulin secretion to stabilize blood glucose.This phenomenon was called insulin resistance(IR).Insulin played a regulatory role in the body through its signaling pathway.If a part of the entire pathway is damaged, the pathway cannot transmit upstream information to the downstream normally, and the regulatory effect of insulin is weakened or even disappears.When IR occurs, insulin is unable to regulate systemic glucose homeostasis if the pathway is compromised.With the development of IR,when the pancreas was unable to provide excess insulin, it leads to a severe imbalance in glucose homeostasis throughout the body.This would be induced T2MD and many metabolic diseases.In recent years, a large number of studies on the pathological mechanism of IR have been reported.The IR induction mechanism of obesity and impaired insulin signaling pathway were focused on this paper, and the relevant research progress were summarized and expound in order to provide ideas and basis for future research.

关 键 词：胰岛素抵抗 肥胖 胰岛素信号通路 2型糖尿病 PI3-K/AKT信号通路 STAT3信号通路 JNK信号通路 

分 类 号：R589.2[医药卫生—内分泌]