Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India.
Department of Endocrinology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India.
Bone. 2023 Nov;176:116884. doi: 10.1016/j.bone.2023.116884. Epub 2023 Aug 18.
Multiple pathogenetic mechanisms are involved in the genesis of various microvascular and macrovascular complications of diabetes mellitus. Of all these, advanced glycation end products (AGEs) have been strongly implicated.
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.
多种发病机制参与了糖尿病各种微血管和大血管并发症的发生。在所有这些机制中，晚期糖基化终产物（AGEs）被强烈暗示与之相关。
本综述旨在总结目前关于 AGEs 产生的文献，并探讨其在糖尿病微血管和大血管并发症发生中的潜在作用。
不受控制的高血糖通过还原糖与蛋白质、脂质或核酸之间的非酶糖基化反应触发 AGEs 的形成。在慢性高血糖下，AGEs 在血液和身体组织中积累。AGEs 会在各种细胞内和细胞外分子之间形成不可逆的交联，并激活晚期糖基化终产物受体（RAGE），这会刺激下游信号通路，产生活性氧（ROS），并导致氧化应激。此外，AGEs 对内质网呼吸链蛋白的细胞内糖化作用也有助于进一步产生 ROS，从而形成一个恶性循环，进一步促进内源性 AGEs 的产生。通过这些途径，AGEs 在各种糖尿病并发症的发病机制中发挥主要作用，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肝疾病。多项临床研究和荟萃分析表明，组织或循环中 AGEs 水平与各种糖尿病并发症的发生呈正相关。此外，外源性 AGEs，主要是来自饮食的 AGEs，会促进胰岛素抵抗、肥胖和代谢综合征。
慢性高血糖引发的 AGEs 在糖尿病各种并发症的发病机制中起着关键作用。
