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靶向糖尿病中的线粒体。

Targeting Mitochondria in Diabetes.

机构信息

Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Faculty of Medicine, University of Belgrade, Dr Subotica 13, 11000 Belgrade, Serbia.

出版信息

Int J Mol Sci. 2021 Jun 21;22(12):6642. doi: 10.3390/ijms22126642.

Abstract

Type 2 diabetes (T2D), one of the most prevalent noncommunicable diseases, is often preceded by insulin resistance (IR), which underlies the inability of tissues to respond to insulin and leads to disturbed metabolic homeostasis. Mitochondria, as a central player in the cellular energy metabolism, are involved in the mechanisms of IR and T2D. Mitochondrial function is affected by insulin resistance in different tissues, among which skeletal muscle and liver have the highest impact on whole-body glucose homeostasis. This review focuses on human studies that assess mitochondrial function in liver, muscle and blood cells in the context of T2D. Furthermore, different interventions targeting mitochondria in IR and T2D are listed, with a selection of studies using respirometry as a measure of mitochondrial function, for better data comparison. Altogether, mitochondrial respiratory capacity appears to be a metabolic indicator since it decreases as the disease progresses but increases after lifestyle (exercise) and pharmacological interventions, together with the improvement in metabolic health. Finally, novel therapeutics developed to target mitochondria have potential for a more integrative therapeutic approach, treating both causative and secondary defects of diabetes.

摘要

2 型糖尿病(T2D)是最常见的非传染性疾病之一,常以前胰岛素抵抗(IR)为前驱,这是组织对胰岛素反应能力丧失的原因,并导致代谢稳态紊乱。线粒体作为细胞能量代谢的核心参与者,参与了 IR 和 T2D 的发生机制。胰岛素抵抗会影响不同组织中的线粒体功能,其中骨骼肌和肝脏对全身葡萄糖稳态的影响最大。本综述重点关注评估 T2D 背景下肝脏、肌肉和血细胞中线粒体功能的人类研究。此外,还列出了针对 IR 和 T2D 中靶向线粒体的不同干预措施,并选择了一些使用呼吸测定法作为线粒体功能衡量标准的研究,以便更好地进行数据比较。总的来说,线粒体呼吸能力似乎是一种代谢指标,因为随着疾病的进展它会降低,但在生活方式(运动)和药物干预后会增加,同时代谢健康状况也会得到改善。最后,为靶向线粒体而开发的新型治疗方法有可能为更具整体性的治疗方法提供治疗糖尿病的病因和继发缺陷的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/837a/8233932/56618196cdfe/ijms-22-06642-g001.jpg

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