video: The animation explains that insulin treatment of patients with diabetes reduces glucose levels, but it causes significant direct damage on the human arteries by activating oxidative stress. Treating patients with a DPP4 inhibitor "sensitizes" the human arteries and makes them respond in the opposite way to insulin, i.e. insulin reduces vascular oxidative stress, becoming from a detrimental to a beneficial intervention. This means that treatment with DPP4 inhibitors may allow insulin treatment to reduce the risk for heart attacks and strokes in diabetics. This material relates to a paper that appeared in the Apr. 29, 2020, issue of Science Translational Medicine, published by AAAS. The paper, by I. Akoumianakis at University of Oxford in Oxford, UK; and colleagues was titled, "Insulin-induced vascular redox dysregulation in human atherosclerosis is ameliorated by dipeptidyl peptidase 4 inhibition." view more
Credit: [Credit: Oxford Translational Cardiovascular Research Group]
通过研究来自674名患者的血管组织，一个研究小组发现了胰岛素是如何促成了动脉粥样硬化（这是全球最常见的慢性健康问题之一）中的血管功能障碍的。他们的研究解释了为什么胰岛素无法治疗糖尿病患者体内的血管损伤，凸显了一种有望纠正胰岛素信号异常并保护血管的替代疗法。胰岛素是体内的一种基本激素，因为它能调节从血糖控制到心血管系统化学反应等过程。II型糖尿病患者通常会有其它慢性疾病（如心脏病和动脉粥样硬化），而研究提示，胰岛素信号异常可能是其肇因。然而，用胰岛素样化合物降低血糖未能减轻糖尿病患者的心血管风险。为了解其原因，Ioannis Akoumianakis和同事检查了674位接受冠状动脉搭桥手术的动脉粥样硬化患者的血管。他们发现，患者的血管对胰岛素具有抵抗力（胰岛素在正常情况下能控制血管的张力），并显示出来自有害氧分子的应激水平升高。高浓度的胰岛素反而与血管内衬细胞中更严重的功能障碍相关。用一种实验性的DPP4酶抑制剂处理血管可减轻氧化应激并恢复正常的胰岛素活性，而用DPP4抑制剂进行长期治疗可在病人和喂以高脂饮食的小鼠体内逆转胰岛素的损伤血管作用。作者得出结论：未来的试验应探索将胰岛素治疗与DPP4抑制剂联合使用以减轻动脉粥样硬化患者血管损伤的可能性。
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Journal
Science Translational Medicine