线粒体基因突变相关的糖尿病研究进展

Research Progress of Diabetes Induced by Mitochondrial DNA Mutations

线粒体是细胞的能量工厂,通过氧化磷酸化以ATP的形式为细胞的各种生命活动提供能量。线粒体基因的突变会导致多种疾病的发生,包括LHON病、耳聋、Ⅱ型糖尿病等。本综述描述了与Ⅱ型糖尿病相关的67种线粒体基因突变,重点讨论了线粒体基因3243、3310、16189、14709、15059、10003位点相应碱基突变与Ⅱ型糖尿病的相关性关系,总结和讨论了线粒体基因突变导致糖尿病发生的具体机制,即线粒体基因突变导致胰岛β细胞氧化磷酸化功能缺陷,ATP产量降低,ADP+含量升高,胰岛素分泌受阻,胰岛素产量降低,机体正常糖代谢受阻从而出现高血糖等二型糖尿病症状。最后,本综述对Ⅱ型糖尿病的诊断方法和治疗手段进行了阐述。

Mitochondria are essential organelles inside cells that are responsible for cellular energy production. Through oxidative phosphorylation, mitochondria provide the energy for cells to conduct various life activities in the form of ATP. The mitochondrial genome has a much higher mutation rate than that observed in nuclear DNA. Mitochondrial DNA （mtDNA） mutations are an important cause of inherited disease including LHON, deafiaess, type 11 diabetes and so on. Here we describe 67mtDNA mutations associated with type 11 diabetes. In detail, we explore mitochondria DNA mutant sites 3243, 3310, 16189, 14709, 15059, 10003 and the specific mechanisms leading to type I1 diabetes. Then, we summarize the mechanism of how these mutations lead to diabetes, that is, specific mtDNA mutations lead to oxidative phosphorylation function defect in islet beta cells, presenting as reduced ATP production and increased ADP＋ content. Thus, insulin secretion is blocked and insulin production is decreased. Finally, the normal metabolism of sugar is frustrated and type 11 diabetes symptoms such as high blood glucose appear. In addition, we elaborate the diagnostic methods and treatments for type 11 diabetes.