Inserm UMR-858, IFR-31, University of Toulouse, France.
Antioxid Redox Signal. 2009 Dec;11(12):3071-109. doi: 10.1089/ars.2009.2484.
Diabetes mellitus is a multifactorial disease, classically influenced by genetic determinants of individual susceptibility and by environmental accelerating factors, such as lifestyle. It is considered a major health concern,as its incidence is increasing at an alarming rate, and the high invalidating effects of its long-term complications affect macro- and microvasculature, heart, kidney, eye, and nerves. Increasing evidence indicates that hyperglycemia is the initiating cause of the tissue damage occurring in diabetes, either through repeated acute changes in cellular glucose metabolism, or through the long-term accumulation of glycated biomolecules and advanced glycation end products (AGEs). AGEs represent a heterogeneous group of chemical products resulting from a nonenzymatic reaction between reducing sugars and proteins, lipids, nucleic acids, or a combination of these.The glycation process (glucose fixation) affects circulating proteins (serum albumin, lipoprotein, insulin, hemoglobin),whereas the formation of AGEs implicates reactive intermediates such as methylglyoxal. AGEs form cross-links on long-lived extracellular matrix proteins or react with their specific receptor RAGE, resulting inoxidative stress and proinflammatory signaling implicated in endothelium dysfunction, arterial stiffening, and microvascular complications. This review summarizes the mechanism of glycation and of AGEs formation and the role of hyperglycemia, AGEs, and oxidative stress in the pathophysiology of diabetic complications.
糖尿病是一种多因素疾病，经典地受个体易感性的遗传决定因素和生活方式等环境加速因素的影响。由于其发病率以惊人的速度增长，并且其长期并发症的高致残影响会影响大血管和微血管、心脏、肾脏、眼睛和神经，因此被认为是一个主要的健康关注点。越来越多的证据表明，高血糖是糖尿病发生组织损伤的起始原因，这既可以通过细胞葡萄糖代谢的反复急性变化，也可以通过糖化生物分子和晚期糖基化终产物（AGEs）的长期积累来实现。AGEs 是由还原糖与蛋白质、脂质、核酸或这些物质的组合之间的非酶反应产生的一组化学物质。糖化过程（葡萄糖固定）会影响循环蛋白（血清白蛋白、脂蛋白、胰岛素、血红蛋白），而 AGEs 的形成则涉及到甲基乙二醛等反应性中间体。AGEs 在寿命长的细胞外基质蛋白上形成交联，或与它们的特定受体 RAGE 反应，导致氧化应激和促炎信号转导，这与内皮功能障碍、动脉僵硬和微血管并发症有关。这篇综述总结了糖化和 AGEs 形成的机制，以及高血糖、AGEs 和氧化应激在糖尿病并发症发病机制中的作用。
