Department of Pharmaceutical Chemistry, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad 44000, Pakistan.
Department of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad 44000, Pakistan.
Int J Biol Macromol. 2023 Aug 30;247:125821. doi: 10.1016/j.ijbiomac.2023.125821. Epub 2023 Jul 17.
Diabetes mellitus causes a wide range of metabolic derangements with multiple organ damage. The microvascular and macrovascular complications of diabetes result partly from the damage to the glycosaminoglycans (GAG) in the basement membrane. GAGs are negatively charged polysaccharides with repeating disaccharide units. They play a significant role in cellular proliferation and signal transduction. Destruction of extracellular matrix results in diseases in various organs including myocardial fibrosis, retinal damage and nephropathy. To substitute the natural GAGs pharmacotherapeutically, they have been synthesized by using basic disaccharide units. Among the four classes of GAGs, heparin is the most widely studied. Recent studies have revealed multiple significant GAG-protein interactions suggesting their use for the management of diabetic complications. Moreover, they can act as biomarkers for assessing the disease progression. A number of GAG-based therapeutic agents are being evaluated for managing diabetic complications. The current review provides an outline of the role of GAGs in diabetes while covering their interaction with different molecular players that can serve as targets for the diagnosis, management and prevention of diabetes and its complications. The medicinal chemistry and clinical pharmacotherapeutics aspects have are covered to aid in the establishment of GAG-based therapies as a possible avenue for diabetes.
糖尿病会引起多种代谢紊乱，导致多器官损伤。糖尿病的微血管和大血管并发症部分是由于基底膜中糖胺聚糖（GAG）的损伤所致。GAG 是带负电荷的多糖，由重复的二糖单位组成。它们在细胞增殖和信号转导中发挥重要作用。细胞外基质的破坏会导致各种器官的疾病，包括心肌纤维化、视网膜损伤和肾病。为了用药物替代天然 GAG，人们已经使用基本的二糖单位对其进行了合成。在四类 GAG 中，肝素是研究最多的一种。最近的研究揭示了多种重要的 GAG-蛋白相互作用，表明它们可用于治疗糖尿病并发症。此外，它们还可以作为评估疾病进展的生物标志物。目前正在评估多种基于 GAG 的治疗药物来治疗糖尿病并发症。本综述概述了 GAG 在糖尿病中的作用，同时涵盖了它们与不同分子靶点的相互作用，这些靶点可作为糖尿病及其并发症的诊断、治疗和预防的靶点。涵盖了药物化学和临床药理学方面的内容，以帮助建立基于 GAG 的治疗方法，作为治疗糖尿病的一种可能途径。
