Kalani Majid
Department of Clinical Sciences, Karolinska Institutet, Dept of Cardiology, Danderyd Hospital, Stockholm, Sweden.
Vasc Health Risk Manag. 2008;4(5):1061-8. doi: 10.2147/vhrm.s3920.
Most of the late diabetic complications such as retinopathy, nephropathy, and neuropathy, have their basis in disturbed microvascular function. Structural and functional changes in the micro-circulation are present in diabetes mellitus irrespective of the organ studied, and the pathogenesis is complex. Endothelial dysfunction, characterized by an imbalance between endothelium-derived vasodilator and vasoconstrictor substances, plays an important role in the pathogenesis of diabetic microangiopathy. Increased circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been found in patients with diabetes, and a positive correlation between plasma ET-1 levels and microangiopathy in patients with type 2 diabetes has been demonstrated. In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production. Vascular endothelial dysfunction may precede insulin resistance, although the feature of insulin resistance syndrome includes factors that have negative effects on endothelial function. Furthermore, ET-1 induces a reduction in insulin sensitivity and may take part in the development of the metabolic syndrome. In the following, the mechanisms by which ET-1 contributes to the development of diabetic microangiopathy and the potentially beneficial effect of selective ET(A) receptor antagonists are discussed.
大多数晚期糖尿病并发症，如视网膜病变、肾病和神经病变，其根源在于微血管功能紊乱。无论研究的是哪个器官，糖尿病患者的微循环都会出现结构和功能变化，且发病机制复杂。内皮功能障碍，其特征为内皮源性血管舒张剂和血管收缩剂之间失衡，在糖尿病微血管病变的发病机制中起重要作用。强效血管收缩肽内皮素-1（ET-1）的循环水平在糖尿病患者中升高，并且已证实2型糖尿病患者血浆ET-1水平与微血管病变之间存在正相关。除了其直接的血管收缩作用外，ET-1水平升高可能通过对一氧化氮（NO）生成的抑制作用导致内皮功能障碍。血管内皮功能障碍可能先于胰岛素抵抗出现，尽管胰岛素抵抗综合征的特征包括对内皮功能有负面影响的因素。此外，ET-1会导致胰岛素敏感性降低，并可能参与代谢综合征的发展。以下将讨论ET-1导致糖尿病微血管病变发展的机制以及选择性ET(A)受体拮抗剂的潜在有益作用。
