The present narrative review aims to summarize the available literature on the genesis of AGEs and their potential role in the causation of both micro- and macrovascular complications of diabetes mellitus.
Uncontrolled hyperglycemia triggers the formation of AGEs through non-enzymatic glycation reactions between reducing sugars and proteins, lipids, or nucleic acids. AGEs accumulate in bloodstream and bodily tissues under chronic hyperglycemia. AGEs create irreversible cross-linkages of various intra- and extracellular molecules and activate the receptor for advanced glycation end products (RAGE), which stimulates downstream signaling pathways that generate reactive oxygen species (ROS) and contribute to oxidative stress. Additionally, intracellular glycation of mitochondrial respiratory chain proteins by AGEs contributes to the further generation of ROS, which, in turn, sets a vicious cycle that further promotes the production of endogenous AGEs. Through these pathways, AGEs play a principal role in the pathogenesis of various diabetic complications, including diabetic retinopathy, nephropathy, neuropathy, bone disease, atherosclerosis and non-alcoholic fatty liver disease. Multiple clinical studies and meta-analyses have revealed a positive association between tissue or circulating levels of AGEs and development of various diabetic complications. Besides, exogenous AGEs, primarily those derived from diets, promote insulin resistance, obesity, and metabolic syndrome.
AGEs, triggered by chronic hyperglycemia, play a pivotal role in the pathogenesis of various complications of diabetes mellitus.
目的:本综述旨在总结有关AGEs的发生及其在糖尿病微血管和大血管并发症中的潜在作用的现有文献。
结果:未控制的高血糖通过还原糖和蛋白质之间的非酶糖基化反应触发AGEs的形成,脂质,或核酸。AGEs在慢性高血糖状态下在血液和身体组织中积累。AGEs产生各种细胞内和细胞外分子的不可逆交联,并激活晚期糖基化终产物(RAGE)的受体,刺激产生活性氧(ROS)并导致氧化应激的下游信号通路。此外,AGEs对线粒体呼吸链蛋白的细胞内糖基化有助于ROS的进一步产生,which,反过来,设定了一个进一步促进内源性AGEs产生的恶性循环。通过这些途径,AGEs在各种糖尿病并发症的发病机制中起主要作用。包括糖尿病视网膜病变,肾病,神经病,骨病,动脉粥样硬化和非酒精性脂肪性肝病。多项临床研究和荟萃分析显示,AGEs的组织或循环水平与各种糖尿病并发症的发展之间存在正相关。此外,外源性AGEs,主要来自饮食,促进胰岛素抵抗,肥胖,和代谢综合征。
结论:AGEs,由慢性高血糖引发,在糖尿病各种并发症的发病机制中起着举足轻重的作用。