Leeds Institute for Cardiovascular and Metabolic Medicine, LIGHT laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
Leeds Institute for Cardiovascular and Metabolic Medicine, LIGHT laboratories, University of Leeds, Clarendon Way, Leeds, LS2 9JT, UK.
Trends Endocrinol Metab. 2016 Feb;27(2):96-104. doi: 10.1016/j.tem.2015.11.009. Epub 2015 Dec 20.
Despite contemporary medical therapy, people with diabetes and insulin resistance experience substantially increased risk of cardiovascular events caused by atherosclerosis. Dysfunction of the endothelium is a key phase in early atherogenesis and represents a promising therapeutic target. The evolutionarily related insulin and insulin-like growth factor-1 (IGF-1) axes are implicated in the development of vascular disease. In this review, we summarise recent developments in our understanding of how modulating the IGF-1 axis influences vascular disease in the setting of insulin resistance. By contrasting data from models of altered insulin and/or IGF-1 signalling, we emphasise the complex spatiotemporal interplay of these systems in health and disease. We then discuss therapeutic opportunities, before detailing important gaps in our knowledge relevant to therapeutic translation.
尽管采用了当代的医学疗法,患有糖尿病和胰岛素抵抗的人群仍面临着由动脉粥样硬化引起的心血管事件风险的显著增加。内皮功能障碍是动脉粥样硬化早期发生的关键阶段,代表了一个有前途的治疗靶点。进化上相关的胰岛素和胰岛素样生长因子-1(IGF-1)轴与血管疾病的发生有关。在这篇综述中,我们总结了最近在理解调节 IGF-1 轴如何影响胰岛素抵抗背景下的血管疾病方面的进展。通过对比胰岛素和/或 IGF-1 信号改变模型中的数据,我们强调了这些系统在健康和疾病中的复杂时空相互作用。然后,我们讨论了治疗机会,最后详细说明了与治疗转化相关的重要知识空白。