林婷^1,,
周乐²,
陈涛^2,3,,
1. 桂林医学院 1. 全科医学院；2. 广西糖尿病系统医学重点实验室；3.基础医学院，广西 桂林 541199
2. 广西糖尿病系统医学重点实验室
3. 基础医学院，广西 桂林 541199

基金项目: 广西壮族自治区区级大学生创新创业训练项目（S202110601083）；桂林医学院博士科研启动基金（20501020049）


详细信息 作者简介: 林 婷（2000-），女，临床医学专业（全科医学方向）2019级本科生。E-mail：3615765727@qq.com



通讯作者: 陈 涛，助理研究员。E-mail：284710790@qq.com 中图分类号: R587.1


摘要:线粒体通过氧化磷酸化以三磷酸腺苷的形式为细胞代谢提供能量。线粒体DNA（mitochondria DNA，mtDNA）突变会导致多种疾病的发生，包括线粒体脑肌病、Leber遗传性视神经病、肌阵挛性癫痫伴破碎红纤维病和2型糖尿病（type 2 diabetes mellitus，T2DM）等。本文综述了与T2DM相关的26个基因的118种线粒体DNA突变，重点分析和讨论线粒体基因组整体突变基因位点及类型、蛋白编码基因突变位点、核糖体核糖核酸（ribosomal ribonucleic acid，rRNA）和转运核糖核酸（transfer ribonucleic acid，tRNA）基因突变位点及二级结构特征和非编码区替代环突变位点与T2DM的相关性及致病机制，即线粒体基因突变导致胰岛β细胞mtDNA拷贝数降低、呼吸链复合物组装受损、rRNA和tRNA结构受损、三磷酸腺苷含量降低、活性氧升高、形成氧化胁迫和线粒体功能受损、胰岛素分泌损伤、糖代谢异常、具有明显的T2DM遗传倾向和胰岛素抵抗，从而导致T2DM的高血糖症状。最后，对mtDNA突变检测在T2DM早期诊断中的作用进行总结。
关键词: 线粒体DNA突变/
2型糖尿病/
早期诊断


Abstract:Mitochondria provides the energy for cell metabolism in the form of adenosine triphosphate through oxidative phosphorylation. Mitochondrial DNA (mtDNA) mutations are an important cause of inherited disease including mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes, Leber′s hereditary optic neuropathy, myoclonic epilepsy with ragged red fibers, type 2 diabetes mellitus (T2DM), etc. In this review, we have described and summarized a total of 118 types of mtDNA mutations in 26 genes associated with T2DM. We will focus on the analysis and discussion of the relationship between whole mitochondrial genome mutation sites and types, protein-coding genes, ribosomal ribonucleic acid (rRNA) and transfer ribonucleic acid (tRNA) genes mutation sites and secondary structure characteristics, displacement loop region mutation sites and types in the non-coding region and T2DM, and the pathogenic mechanisms, that is mitochondrial gene mutations leading to decreased islets β cell mtDNA copy number, damaged respiratory chain complex assembly, damaged rRNA and tRNA secondary structure, decreased adenosine triphosphate content, increased reactive oxygen species, impaired oxidative stress and mitochondrial function, abnormal insulin secretion and glucose metabolism, obvious T2DM genetic tendency and insulin resistance, eventually resulting in hyperglycemia symptoms in T2DM patients. Finally, we will expound on the role of mtDNA mutation detection in early diagnosis of T2DM.
Keywords:mitochondria DNA mutations/
type 2 diabetes mellitus/
early diagnosis

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https://journal.dmu.edu.cn/data/article/export-pdf?id=640aa3f3fa89b2af1f872521