Burgos-Morón Estefania, Abad-Jiménez Zaida, Marañón Aranzazu Martínez de, Iannantuoni Francesca, Escribano-López Irene, López-Domènech Sandra, Salom Christian, Jover Ana, Mora Vicente, Roldan Ildefonso, Solá Eva, Rocha Milagros, Víctor Víctor M
Service of Endocrinology, University Hospital Doctor Peset - Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain.
Service of Cardiology, University Hospital Doctor Peset - Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46017 Valencia, Spain.
J Clin Med. 2019 Sep 4;8(9):1385. doi: 10.3390/jcm8091385.
Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic β-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.
2型糖尿病（T2D）是一种以高血糖和胰岛素抵抗为特征的代谢紊乱疾病，其中氧化应激被认为是主要病因。鉴于线粒体是活性氧（ROS）的主要来源，我们着手对氧化应激如何产生以及与T2D的关系进行总体概述。由于葡萄糖过载和氧化磷酸化，线粒体中活性氧（ROS）生成增加且发生氧化应激。内质网（ER）应激在氧化应激中起重要作用，因为它也是活性氧的来源。通过线粒体相关膜（MAMs），这两个细胞器之间紧密的相互联系意味着线粒体中产生的活性氧会促进内质网应激。因此，应激状态和线粒体功能障碍是这个恶性循环的结果。线粒体在胰岛素释放中的作用以及胰腺β细胞暴露于高血糖环境使它们特别容易受到氧化应激和线粒体功能障碍的影响。事实上，这两种机制之间的相互作用与葡萄糖稳态的改变有关，并可导致与糖尿病相关的胰岛素抵抗状态。在本综述中，我们讨论了目前关于T2D中氧化应激、线粒体、内质网应激、炎症和脂毒性之间关系的知识。
