Insulin resistance and endothelial cell dysfunction: studies in mammalian models
Insulin resistance and endothelial cell dysfunction: studies in mammalian models
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DOI：
10.1113/expphysiol.2007.039172
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发表时间：
2008-01-01
影响因子：
2.7
通讯作者：
Wheatcroft, Stephen B.
中科院分区：
文献类型：
--
作者：
Kearney, Mark T.;Duncan, Edward R.;Wheatcroft, Stephen B.
2型糖尿病和肥胖是心血管动脉粥样硬化发生的主要危险因素。抵抗胰岛素对其传统靶组织（肌肉、肝脏和脂肪组织）的代谢作用是这些疾病的主要致病特征。然而，胰岛素抵抗在非规范组织（如内皮）中的作用尚不清楚。几项大型研究支持胰岛素抵抗在独立于2型糖尿病和肥胖的过早心血管动脉粥样硬化发展中的作用。动脉粥样硬化发生和发展的一个关键步骤是内皮细胞来源的一氧化氮生物活性的降低。一氧化氮是一种信号分子，具有一系列潜在的抗动脉粥样硬化作用。胰岛素受体在内皮细胞上的存在是有充分证据的，内皮现在已经成为胰岛素潜在的重要靶组织，胰岛素刺激一氧化氮的产生是胰岛素对内皮细胞作用的一个特征。内皮细胞水平的胰岛素抵抗在血管病理生理中的作用尚不清楚。对人类和基因修饰小鼠的大量研究表明，胰岛素抵抗和一氧化氮生物活性之间存在密切联系。在这篇综述中，我们讨论了人类胰岛素抵抗和内皮细胞功能之间的联系，并展示了肥胖和胰岛素抵抗的小鼠模型在我们理解与2型糖尿病和肥胖相关的血管病变方面提供的补充信息。
Type 2 diabetes and obesity are major risk factors for the development of cardiovascular atherosclerosis. Resistance to the metabolic effects of insulin on its traditional target tissues (muscle, liver and adipose tissue) is a central pathogenic feature of these disorders. However, the role of insulin resistance in non-canonical tissues, such as the endothelium, is less clear. Several large studies support a role for insulin resistance in the development of premature cardiovascular atherosclerosis independent of type 2 diabetes and obesity. A key step in the initiation and progression of atherosclerosis is a reduction in the bioactivity of endothelial cell-derived nitric oxide. Nitric oxide is a signalling molecule which has a portfolio of potential antiatherosclerotic effects. The presence of insulin receptors on endothelial cells is well documented, and the endothelium has now emerged as a potentially important target tissue for insulin, with insulin-stimulated production of nitric oxide a feature of the action of insulin on endothelial cells. The role of insulin resistance at the level of the endothelial cell in vascular pathophysiology is unclear. A number of studies in humans and gene-modified mice have demonstrated a close association between insulin resistance and nitric oxide bioactivity. In this review, we discuss the link between insulin resistance and endothelial cell function in humans and demonstrate the complimentary information provided by murine models of obesity and insulin resistance in our understanding of the vasculopathy associated with type 2 diabetes and obesity.