Hermans M P
Service d'Endocrinologie & Nutrition, Cliniques universitaires St-Luc, 54, avenue Hippocrate, 1200 Bruxelles, Belgique.
Acta Clin Belg. 2007 Mar-Apr;62(2):97-101. doi: 10.1179/acb.2007.017.
Abnormal endothelial function plays a pivota role in the pathogenesis of diabetic complications. Due to lack of autoregulation of glucose transport in the presence of high extracellular glucose concentrations, intracellular hyperglycaemia induces a series of metabolic changes that ultimately lead to the genesis of both microvascular complications (the hallmark of chronic hyperglycaemic states) and macrovascular damage. In type 2 diabetes, the abnormalities associated with insulin resistance and the metabolic syndrome phenotype (such as high blood pressure, dyslipidaemia, abnormal levels of circulating adipokines and free fatty acids e.g.) also contribute to accelerate the endothelial damage sustained as a result of chronic exposure to hyperglycaemia. Only recently was a unifying theory proposed to account for the four major abnormal pathways activated by chronic hyperglycaemia and thought to damage the endothelial cell and to trigger the downstream micro- and macrovascular complications associated with diabetes mellitus. This pathophysiological sequence revolves around the metabolic abnormalities triggered as a result of overproduction of superoxide by the mitochondrial electron transport chain and subsequent inhibition of the key glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase by increased activity of nuclear poly(ADP-ribose)polymerase.
内皮功能异常在糖尿病并发症的发病机制中起关键作用。由于在细胞外葡萄糖浓度高时缺乏葡萄糖转运的自动调节，细胞内高血糖会引发一系列代谢变化，最终导致微血管并发症（慢性高血糖状态的标志）和大血管损伤的发生。在2型糖尿病中，与胰岛素抵抗和代谢综合征表型相关的异常（如高血压、血脂异常、循环中脂肪因子和游离脂肪酸水平异常等）也会加速因长期暴露于高血糖而导致的内皮损伤。直到最近才提出了一个统一的理论来解释慢性高血糖激活的四条主要异常途径，这些途径被认为会损害内皮细胞并引发与糖尿病相关的下游微血管和大血管并发症。这个病理生理过程围绕着线粒体电子传递链超氧化物过度产生以及随后核聚（ADP-核糖）聚合酶活性增加抑制关键糖酵解酶甘油醛-3-磷酸脱氢酶所引发的代谢异常展开。
