Jansson P-A
Lundberg Laboratory for Diabetes Research, Department of Molecular and Clinical Medicine/Diabetes, The Sahlgrenska Academy at Göteborg University, Sahlgrenska University Hospital, Sahlgrenska S-413 45, Göteborg, Sweden.
J Intern Med. 2007 Aug;262(2):173-83. doi: 10.1111/j.1365-2796.2007.01830.x.
Macrovascular disease is the number one killer in type 2 diabetes patients. The cluster of risk factors in the insulin resistance syndrome (IRS) partly explains this notion. Insulin action in muscle, liver or adipose tissue has been thoroughly described in the literature, whilst this has been less described for the endothelium. Insulin stimulates nitric oxide (NO) production in the endothelium and reduced bioavailability of NO is usually defined as endothelial dysfunction. This impairment might be related to defective insulin signalling in the endothelial cell. Therefore, insulin resistance mechanisms in the endothelial cell will be emphasized in this review. Imbalance between the vasodilating agent NO and the vasoconstrictor endothelin-1 (ET-1) contributes to endothelial dysfunction. Different methods and circulating markers to assess endothelial function will be outlined. Circulating markers of an activated endothelium appear long before type 2 diabetes develops suggesting a unique role of the endothelium in the pathophysiology of the disease. Hampered blood flow in nutritive capillaries due to endothelial dysfunction is coupled with decreased glucose uptake and hyperglycemia. The forearm model combined with muscle microdialysis enables us to measure interstitial glucose and an index for capillary recruitment, the permeability surface area (PS). Available data from this method suggest that capillary recruitment in response of insulin is impaired in insulin resistant human subjects.
大血管疾病是2型糖尿病患者的首要死因。胰岛素抵抗综合征（IRS）中的危险因素群部分解释了这一现象。肌肉、肝脏或脂肪组织中的胰岛素作用在文献中已有详尽描述，而内皮中的胰岛素作用描述较少。胰岛素刺激内皮细胞产生一氧化氮（NO），NO生物利用度降低通常被定义为内皮功能障碍。这种损害可能与内皮细胞中胰岛素信号传导缺陷有关。因此，本综述将重点关注内皮细胞中的胰岛素抵抗机制。血管舒张剂NO与血管收缩剂内皮素-1（ET-1）之间的失衡导致内皮功能障碍。将概述评估内皮功能的不同方法和循环标志物。在2型糖尿病发生之前，活化内皮的循环标志物就已出现，这表明内皮在该疾病的病理生理学中具有独特作用。内皮功能障碍导致营养性毛细血管血流受阻，进而导致葡萄糖摄取减少和高血糖。前臂模型结合肌肉微透析使我们能够测量组织间葡萄糖和毛细血管募集指数——通透表面积（PS）。该方法的现有数据表明，胰岛素抵抗的人类受试者对胰岛素反应的毛细血管募集受损。
