Myocardial infarction is sufficient to increase GLP-1 secretion, leading to improved left ventricular contractility and mitochondrial respiratory capacity
Myocardial infarction is sufficient to increase GLP-1 secretion, leading to improved left ventricular contractility and mitochondrial respiratory capacity
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DOI：
10.1111/dom.13472
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发表时间：
2018-12-01
影响因子：
5.8
通讯作者：
Lehrke, Michael
中科院分区：
文献类型：
--
作者：
Diebold, Sebastian;Moellmann, Julia;Lehrke, Michael
心肌梗死引起左心室功能的快速损害，需要非梗死组织区域的超收缩反应来维持血流动力学的稳定。这种代偿性适应是由体液、炎症和神经元信号介导的。GLP-1是一种具有血糖调节和心脏保护能力的肠促胰岛素，在营养和炎症刺激下分泌。GLP-1的失活是由普遍存在的酶DPP-4引起的。本研究通过心肌梗死后外周血GLP-1浓度的测定，并结合代谢、左心室收缩力和线粒体功能进行评价。急性心肌梗死患者循环GLP-1浓度明显升高。永久性LAD结扎引起的实验性心肌梗死足以增加小鼠GLP-1的分泌。这是以时间依赖的方式发生的，这与利格列汀抑制DPP-4的能力相吻合，以GLP-1受体依赖的方式增强左心室收缩力。机制上，DPP-4抑制增加AMPK活性并刺激非梗死组织区域的线粒体呼吸能力。我们描述了心肌梗死期间炎性GLP-1分泌与左心室收缩力的新功能相关性。
Myocardial infarction causes rapid impairment of left ventricular function and requires a hypercontractile response of non-infarcted tissue areas to maintain haemodynamic stability. This compensatory adaptation is mediated by humoral, inflammatory and neuronal signals. GLP-1 is an incretin hormone with glucoregulatory and cardioprotective capacities and is secreted in response to nutritional and inflammatory stimuli. Inactivation of GLP-1 is caused by the ubiquitously present enzyme DPP-4. In this study, circulating concentrations of GLP-1 were assessed after myocardial infarction and were evaluated in the light of metabolism, left ventricular contractility and mitochondrial function. Circulating GLP-1 concentrations were markedly increased in patients with acute myocardial infarction. Experimental myocardial infarction by permanent LAD ligation proved sufficient to increase GLP-1 secretion in mice. This took place in a time-dependent manner, which coincided with the capacity of DPP-4 inhibition, by linagliptin, to augment left ventricular contractility in a GLP-1 receptor-dependent manner. Mechanistically, DPP-4 inhibition increased AMPK activity and stimulated the mitochondrial respiratory capacity of non-infarcted tissue areas. We describe a new functional relevance of inflammatory GLP-1 secretion for left ventricular contractility during myocardial infarction.