Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Rev Endocr Metab Disord. 2013 Mar;14(1):87-99. doi: 10.1007/s11154-013-9237-9.
Insulin resistance affects the vascular endothelium, and contributes to systemic insulin resistance by directly impairing the actions of insulin to redistribute blood flow as part of its normal actions driving muscle glucose uptake. Impaired vascular function is a component of the insulin resistance syndrome, and is a feature of type 2 diabetes. On this basis, the vascular endothelium has emerged as a therapeutic target where the intent is to improve systemic metabolic state by improving vascular function. We review the available literature presenting studies in humans, evaluating the effects of metabolically targeted and vascular targeted therapies on insulin action and systemic metabolism. Therapies that improve systemic insulin resistance exert strong concurrent effects to improve vascular function and vascular insulin action. RAS-acting agents and statins have widely recognized beneficial effects on vascular function but have not uniformly produced the hoped-for metabolic benefits. These observations support the notion that systemic metabolic benefits can arise from therapies targeted at the endothelium, but improving vascular insulin action does not result from all treatments that improve endothelium-dependent vasodilation. A better understanding of the mechanisms of insulin's actions in the vascular wall will advance our understanding of the specificity of these responses, and allow us to better target the vasculature for metabolic benefits.
胰岛素抵抗会影响血管内皮，并且通过直接损害胰岛素重新分配血流的作用来导致全身胰岛素抵抗，这是胰岛素发挥正常作用以促进肌肉葡萄糖摄取的一部分。血管功能障碍是胰岛素抵抗综合征的一个组成部分，也是 2 型糖尿病的一个特征。在此基础上，血管内皮已成为一个治疗靶点，其目的是通过改善血管功能来改善全身代谢状态。我们回顾了现有的文献，评估了针对代谢和血管的靶向治疗对胰岛素作用和全身代谢的影响。改善全身胰岛素抵抗的治疗方法对血管功能和血管胰岛素作用具有强烈的协同作用。作用于肾素-血管紧张素系统的药物和他汀类药物对血管功能具有广泛公认的有益作用，但并未产生预期的代谢益处。这些观察结果支持这样一种观点，即针对内皮的治疗可以带来全身代谢益处，但并非所有改善内皮依赖性血管舒张的治疗都能改善血管胰岛素作用。对胰岛素在血管壁中作用机制的更好理解将增进我们对这些反应特异性的理解，并使我们能够更好地针对血管以获得代谢益处。
