Laboratory of Glycation Biology and Metabolic Disorders, IIRC-1, Integral University, Lucknow, U.P.. India.
Department of Bio-sciences, Integral University, Lucknow , UP. India.
Curr Vasc Pharmacol. 2017;15(4):352-364. doi: 10.2174/1570161115666170327162639.
In diabetic patients, accelerated glycation process causes increased oxidative stress and chronic hyperglycaemia that play a vital role in the diabetic complications. Extensive intracellular and extracellular generation of these glycated products finally form advanced glycation end products (AGEs). The accumulation of AGEs is related with the intensive risk for microvascular and macrovascular injuries for diabetic patients. Therefore, formation of AGEs results from the condensation of reducing sugars with biomolecules like nucleic acids, proteins, and lipids which potentially alter their function. Effect of AGEs formation is also related with the cross-linking that promotes vascular stiffness which modifies the vascular structure and long-life function of proteins. Formation of AGEs may also activate specific receptors, like receptor for AGEs (RAGEs) that induce the intracellular signaling which enhance the oxidative stress and also the amplification of key pro-sclerotic and pro-inflammatory cytokines. From last few decades, a huge number of pre-clinical studies related with the AGEs formation in the diabetic patients have been performed. The target for such trials was the formation and degradation of AGEs, and its interaction with RAGEs. This review focuses on the mechanism how these AGEs exert detrimental nuisance in the diabetes, as well as deal with existing strategies to disrupt the action or formation of AGEs. Therefore, the unseen role of both the early and advanced stage glycation in the diabetic Vasculopathy is described. We have also illustrated how the glycation inhibition results in the delay of the development of vascular complications in diabetic patients.
在糖尿病患者中，糖化过程加速导致氧化应激增加和慢性高血糖，这在糖尿病并发症中起着至关重要的作用。这些糖化产物在细胞内和细胞外的广泛产生最终形成晚期糖基化终末产物（AGEs）。AGEs 的积累与糖尿病患者微血管和大血管损伤的高风险密切相关。因此，AGEs 的形成是由于还原糖与核酸、蛋白质和脂质等生物分子的缩合，这些生物分子的功能可能会发生改变。AGEs 形成的影响也与促进血管僵硬的交联有关，交联会改变血管结构和蛋白质的长寿命功能。AGEs 的形成也可能激活特定的受体，如 AGEs 受体（RAGEs），诱导细胞内信号增强氧化应激，放大关键的促硬化和促炎细胞因子。在过去的几十年中，已经进行了大量与糖尿病患者 AGEs 形成相关的临床前研究。这些试验的目的是 AGEs 的形成和降解，以及它与 RAGEs 的相互作用。这篇综述重点介绍了这些 AGEs 在糖尿病中产生有害影响的机制，以及现有的破坏 AGEs 作用或形成的策略。因此，描述了早期和晚期糖基化在糖尿病血管病变中的未知作用。我们还说明了糖基化抑制如何导致糖尿病患者血管并发症的发展延迟。
