Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA.
Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ, USA.
J Mol Cell Biol. 2021 Oct 21;13(7):500-512. doi: 10.1093/jmcb/mjab024.
Endothelium, acting as a barrier, protects tissues against factors that provoke insulin resistance and type 2 diabetes and itself responds to the insult of insulin resistance inducers with altered function. Endothelial insulin resistance and vascular dysfunction occur early in the evolution of insulin resistance-related disease, can co-exist with and even contribute to the development of metabolic insulin resistance, and promote vascular complications in those affected. The impact of endothelial insulin resistance and vascular dysfunction varies depending on the blood vessel size and location, resulting in decreased arterial plasticity, increased atherosclerosis and vascular resistance, and decreased tissue perfusion. Women with insulin resistance and diabetes are disproportionately impacted by cardiovascular disease, likely related to differential sex-hormone endothelium effects. Thus, reducing endothelial insulin resistance and improving endothelial function in the conduit arteries may reduce atherosclerotic complications, in the resistance arteries lead to better blood pressure control, and in the microvasculature lead to less microvascular complications and more effective tissue perfusion. Multiple diabetes therapeutic modalities, including medications and exercise training, improve endothelial insulin action and vascular function. This action may delay the onset of type 2 diabetes and/or its complications, making the vascular endothelium an attractive therapeutic target for type 2 diabetes and potentially type 1 diabetes.
内皮细胞作为一道屏障，保护组织免受引发胰岛素抵抗和 2 型糖尿病的因素的侵害，同时自身也会对胰岛素抵抗诱导因素的侵害做出反应，导致功能改变。内皮细胞胰岛素抵抗和血管功能障碍在与胰岛素抵抗相关疾病的演变早期就已经出现，它们可以同时存在，甚至有助于代谢性胰岛素抵抗的发展，并促进受影响者的血管并发症。内皮细胞胰岛素抵抗和血管功能障碍的影响因血管大小和位置的不同而有所不同，导致动脉弹性降低、动脉粥样硬化和血管阻力增加，以及组织灌注减少。胰岛素抵抗和糖尿病女性受心血管疾病的影响不成比例，这可能与性激素对内皮细胞的不同作用有关。因此，减少内皮细胞胰岛素抵抗和改善输送动脉的内皮功能可能会减少动脉粥样硬化并发症，在阻力血管中导致更好的血压控制，在微血管中导致更少的微血管并发症和更有效的组织灌注。多种糖尿病治疗方法，包括药物治疗和运动训练，都可以改善内皮细胞的胰岛素作用和血管功能。这种作用可能会延迟 2 型糖尿病及其并发症的发生，使血管内皮成为 2 型糖尿病甚至 1 型糖尿病有吸引力的治疗靶点。
