摘要
2型糖尿病(T2DM)是临床常见的内分泌紊乱疾病之一,以胰岛素抵抗和胰岛素分泌不足为主要病理特征。T2DM致病机制复杂,其与内质网应激(ERS)、线粒体氧化应激、细胞凋亡等密切相关,但具体机制尚未明确。内质网-线粒体结构偶联又称线粒体相关内质网膜(MAM),对细胞内钙离子(Ca^(2+))分布有着直接或间接的调控作用,且Ca^(2+)对于细胞内环境的稳态具有重要意义。持续的ERS导致MAM结构受损,使其调控内质网、线粒体释放和摄取Ca^(2+)的能力下降。线粒体中过度蓄积的Ca^(2+)会激活氧化应激,加剧ERS,进而启动胰岛β细胞的凋亡程序。在外周组织中发生ERS则会产生胰岛素抵抗,最终导致T2DM的发生与发展。该文介绍了在ERS过程中MAM结构的调控作用以及与胰岛素抵抗发生的关联性,为T2DM的临床治疗和致病机制的探究提供了依据。
Type 2 diabetes mellitus(T2DM)is one of the common clinical endocrine disorders,insulin resistance and insulin deficiency are the two most characteristic pathological features of T2DM.The pathogenesis of T2DM are complex.Endoplasmic reticulum stress(ERS),mitochondrial oxidative stress,apoptosis and other mechanisms were closely related to the pathogenesis of T2DM,whereas the specifically pathogenesis is unclear.The endoplasmic reticulum-mitochondrial structure coupling also known as mitochondria-associated ER membranes(MAM),has a direct or indirect regulation on intracellular calcium(Ca^(2+))distribution,and the distribution of Ca^(2+)has great significance to the stability of the intracellular environment.Persistent ERS results in structure damage to MAM,reducing the ability of MAM for regulating the endoplasmic reticulum and mitochondrial to release and uptake Ca^(2+).Excessive accumulation of Ca^(2+)in mitochondria activates oxidative stress,exacerbates ERS,and then initiates the apoptotic process of isletβcell.ERS in peripheral tissues can lead to insulin resisitance.The above causes eventually lead to the occurrence and development of T2DM.This article describes the regulatory role of the MAM structure in ERS and its association with the pathogenesis of insulin resistance,and provides the basis to explore the clinical treatment and pathogenesis of T2DM.
作者
刘慧宇
李汶
刘子璇
李肖
黄延芹
LIU Huiyu;LI Wen;LIU Zixuan;LI Xiao;HUANG Yanqin(College of Traditional Chinese Medicine,Shandong University of Traditional Chinese Medicine,Shandong 250014,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Shandong 250014,China)
出处
《激光生物学报》
CAS
2022年第2期97-103,共7页
Acta Laser Biology Sinica
基金
国家自然科学基金项目(81974562,81603613)
济南市科技创新计划项目(202019029)
山东省泰山学者工程专项项目(ts201712097)。
关键词
2型糖尿病
内质网应激
线粒体相关内质网膜
氧化应激
钙离子
type 2 diabetes mellitus
endoplasmic reticulum stress
mitochondria-associated ER membranes
oxidative stress
calcium
