Endothelial dysfunction: Cause of the insulin resistance syndrome
Endothelial dysfunction: Cause of the insulin resistance syndrome
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DOI：
10.2337/diab.46.2.s9
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发表时间：
1997-09-01
期刊：
影响因子：
7.7
通讯作者：
Yudkin, JS
中科院分区：
文献类型：
--
作者：
Pinkney, JH;Stehouwer, CDA;Yudkin, JS
胰岛素抵抗被认为是动脉粥样硬化形成的代谢基础。这一假说基于“胰岛素抵抗综合征”的概念，根据该概念，胰岛素抵抗被视为引起血脂异常、原发性高血压、糖耐量受损和NIDDM的主要异常。然而，这一假说没有考虑到血管内皮在致动脉粥样硬化过程中的重要作用。虽然内皮损伤是动脉粥样硬化形成的早期和突出特征，但对其代谢后果的关注相对较少。在NIDDM受试者中，我们已经证明内皮功能障碍与胰岛素抵抗相关，提出了这种关系是否可能是因果关系的问题。在这篇文章中，我们审查的因素，被认为是负责的发展过程中动脉粥样硬化的内皮功能障碍，以及内皮功能障碍的代谢后果。虽然在大，中型动脉内皮功能障碍起着核心作用的动脉粥样硬化，我们认为，外周血管内皮功能障碍，在小动脉和毛细血管水平，发挥主要作用的发病机制，胰岛素抵抗和相关功能的胰岛素抵抗综合征。我们认为胰岛素抵抗综合征和动脉粥样硬化形成的许多方面可以被看作是不同血管床内皮功能障碍的不同后果。这一新的和可检验的假说解释了与动脉粥样硬化形成相关的内皮和代谢异常。
Insulin resistance has been proposed as the metabolic basis of atherogenesis. This hypothesis is based on the concept of the ''insulin resistance syndrome,'' according to which insulin resistance is viewed as the primary abnormality that gives rise to dyslipidemia, essential hypertension, impaired glucose tolerance, and NIDDM. However, this hypothesis takes no account of the well established and central role of vascular endothelium in the atherogenic process. Although endothelial injury is an early and prominent feature of atherogenesis, relatively little attention has been given to its metabolic consequences. In subjects with NIDDM, we have shown that endothelial dysfunction is associated with insulin resistance, raising the question of whether this relationship could be causal. In this article, we review the factors that are considered to be responsible for the development of endothelial dysfunction during atherogenesis, together with the metabolic consequences of endothelial dysfunction. While dysfunction of the endothelium in large and medium-sized arteries plays a central role in atherogenesis, we argue that dysfunction of peripheral vascular endothelium, at arteriolar and capillary level, plays the primary role in the pathogenesis of both insulin resistance and the associated features of the insulin resistance syndrome. We propose that the insulin resistance syndrome, together with many aspects of atherogenesis, can be viewed as the diverse consequences of endothelial dysfunction in different vascular beds. This new and testable hypothesis accounts for both the endothelial and metabolic abnormalities associated with atherogenesis.