Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, Canada.
Semin Thromb Hemost. 2021 Apr;47(3):261-273. doi: 10.1055/s-0041-1724118. Epub 2021 Apr 1.
Diabetes is a complex disorder responsible for the mortality and morbidity of millions of individuals worldwide. Although many approaches have been used to understand and treat diabetes, the role of proteoglycans, in particular heparan sulfate proteoglycans (HSPGs), has only recently received attention. The HSPGs are heterogeneous, highly negatively charged, and are found in all cells primarily attached to the plasma membrane or present in the extracellular matrix (ECM). HSPGs are involved in development, cell migration, signal transduction, hemostasis, inflammation, and antiviral activity, and regulate cytokines, chemokines, growth factors, and enzymes. Hyperglycemia, accompanying diabetes, increases reactive oxygen species and upregulates the enzyme heparanase that degrades HSPGs or affects the synthesis of the HSPGs altering their structure. The modified HSPGs in the endothelium and ECM in the blood vessel wall contribute to the nephropathy, cardiovascular disease, and retinopathy seen in diabetes. Besides the blood vessel, other cells and tissues in the heart, kidney, and eye are affected by diabetes. Although not well understood, the adipose tissue, intestine, and brain also reveal HSPG changes associated with diabetes. Further, HSPGs are significantly involved in protecting the β cells of the pancreas from autoimmune destruction and could be a focus of prevention of type I diabetes. In some circumstances, HSPGs may contribute to the pathology of the disease. Understanding the role of HSPGs and how they are modified by diabetes may lead to new treatments as well as preventative measures to reduce the morbidity and mortality associated with this complex condition.
糖尿病是一种复杂的疾病，导致了全世界数百万人的死亡和发病。尽管已经采用了许多方法来理解和治疗糖尿病，但糖胺聚糖，特别是硫酸乙酰肝素蛋白聚糖（HSPGs）的作用最近才受到关注。HSPGs 是异质的、高度带负电荷的，存在于所有细胞中，主要附着在质膜上或存在于细胞外基质（ECM）中。HSPGs 参与发育、细胞迁移、信号转导、止血、炎症和抗病毒活性，并调节细胞因子、趋化因子、生长因子和酶。伴随糖尿病的高血糖会增加活性氧，并上调降解 HSPGs 的酶肝素酶，或影响 HSPGs 的合成，改变其结构。血管壁内皮细胞和 ECM 中修饰的 HSPGs 导致糖尿病中所见的肾病、心血管疾病和视网膜病变。除了血管，心脏、肾脏和眼睛的其他细胞和组织也受到糖尿病的影响。尽管还不太清楚，但脂肪组织、肠道和大脑也显示出与糖尿病相关的 HSPG 变化。此外，HSPGs 对保护胰腺的β细胞免受自身免疫破坏有重要作用，可能成为预防 1 型糖尿病的重点。在某些情况下，HSPGs 可能会导致疾病的病理变化。了解 HSPGs 的作用以及它们如何被糖尿病修饰，可能会带来新的治疗方法以及预防措施，以降低与这种复杂疾病相关的发病率和死亡率。
