Qaed Eskandar, Aldahmash Waleed, Mahyoub Mueataz A
Collage of Pharmacy, Department of Pharmacology, Dalian Medical University, Dalian, 116044, China.
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, P. R. China.
Glycoconj J. 2025 Sep 22. doi: 10.1007/s10719-025-10194-x.
Diabetes mellitus (DM) is marked by prolonged elevated blood glucose levels, which lead to the formation of covalent adducts between glucose and plasma proteins through a non-enzymatic reaction called glycation. This biochemical process plays a crucial role in the development of DM complications, including retinopathy, nephropathy, neuropathy, and cardiomyopathy, while also impacting conditions such as rheumatoid arthritis, osteoporosis, and aging. Glycation alters the molecular structure, enzymatic activity, and receptor interactions of proteins, affecting their normal functions. Advanced glycation end products (AGEs) arise from these modifications, forming cross-links within and between cells, which affect proteins and other vital biomolecules, such as lipids and nucleic acids. This contributes significantly to the complex complications associated with DM. Recent studies highlight the interaction between AGEs and their specific receptors, receptor for advanced glycation end products (RAGE), located on the plasma membrane. This involvement initiates changes in intracellular signaling, alters gene expression, and stimulates the release of pro-inflammatory cytokines and reactive oxygen species. This review examines the glycation of key plasma proteins albumin, fibrinogen, globulins, and collagen and discusses the various AGEs formed. Furthermore, it elucidates the role of AGEs in the exacerbation of DM complications, providing a comprehensive overview of the molecular pathways involved and the systemic impact of these glycation products.
糖尿病（DM）的特征是血糖水平长期升高，这会通过一种称为糖基化的非酶促反应导致葡萄糖与血浆蛋白之间形成共价加合物。这一生物化学过程在糖尿病并发症（包括视网膜病变、肾病、神经病变和心肌病）的发展中起着关键作用，同时也会影响类风湿性关节炎、骨质疏松症和衰老等病症。糖基化会改变蛋白质的分子结构、酶活性和受体相互作用，影响其正常功能。这些修饰会产生晚期糖基化终末产物（AGEs），在细胞内和细胞间形成交联，从而影响蛋白质和其他重要生物分子，如脂质和核酸。这对与糖尿病相关的复杂并发症有显著影响。最近的研究强调了AGEs与其位于质膜上的特异性受体——晚期糖基化终末产物受体（RAGE）之间的相互作用。这种相互作用引发细胞内信号传导的变化，改变基因表达，并刺激促炎细胞因子和活性氧的释放。本综述研究了关键血浆蛋白白蛋白、纤维蛋白原、球蛋白和胶原蛋白的糖基化，并讨论了形成的各种AGEs。此外，它阐明了AGEs在糖尿病并发症加重中的作用，全面概述了相关的分子途径以及这些糖基化产物的全身影响。
