Investigation of the ability of GLP-1 to protect the left ventricle during myocardial ischaemia

心脏病是糖尿病患者最常见的死亡原因，2型糖尿病（T2 DM）和冠状动脉疾病（CAD）的组合是过早心血管发病率和死亡率的主要原因。通过心脏改善葡萄糖代谢的疗法尚未被广泛采用，因为它们繁琐，提供的益处有限，因此尚未在临床实践中被广泛采用。这项拟议的研究建立在英国心脏基金会和MRC的现有资金基础上，以评估代谢因素的影响，以提高心脏耐受冠状动脉疾病（缺血，临床上被认为是心绞痛）导致的血液供应减少的影响的能力。最近发现主要由上肠响应食物分泌的肽，胰高血糖素样肽1（GLP-1），改善T2 DM患者中胰岛素的作用并改善葡萄糖代谢。目前，许多限制这种肽分解的药物已被批准用于治疗2型糖尿病，拟议的研究将调查增加血液中GLP-1的水平是否能提高心脏耐受缺血的能力。我们的初步结果表明，GLP-1确实能保护心脏免受缺血期间和缺血后发生的收缩功能障碍。此外，在少数接受冠状动脉血管成形术和支架植入术的患者中进行的初步研究表明，输注GLP-1可在治疗过程中保护心脏，这在T2 DM患者中尤其重要。该研究将提供信息，允许测试更安全的代谢治疗的疗效，并确认T2 DM患者的疗效，将提供有关治疗效果介导的新信息，并为CAD和T2 DM患者的后续干预性研究提供基础。

Heart disease is the most common cause of death in patients with diabetes mellitus, and the combination of type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) is a major cause of premature cardiovascular morbidity and mortality. Therapy to improve glucose metabolism by the heart have not been widely adopted as they are cumbersome, offer limited benefit and have therefore not been widely adopted in clinical practice. This proposed research builds on existing funding from the British Heart Foundation and the MRC to assess the effect of metabolic factors to improve the ability of the heart to tolerate the effects of a reduced blood supply due to coronary artery disease (ischaemia, clinically recognised as angina). A peptide, glucagon-like peptide 1 (GLP-1), that is secreted mainly by upper intestine in response to food has recently been found to improve the action of insulin in patients with T2DM and improve glucose metabolism. A number of drugs that limit the breakdown of this peptide have now been licensed to treat T2DM, and the proposed research will investigate whether increasing the level of GLP-1 in the blood improves the ability of the heart to tolerate ischaemia.Our preliminary results suggest that GLP-1 does indeed protect the heart against contractile dysfunction that occurs both during and after ischaemia. I addition, pilot studies in a small number of patients undergoing coronary angioplasty and stenting suggest that an infusion of GLP-1 protects the heart during the therapeutic procedure, which is particularly important in those with T2DM. The research will be informative by allowing the efficacy of a safer metabolic therapy to be tested and confirmation of efficacy in patients with T2DM will provide novel information about the mediation of a therapeutic effect and provide the basis for subsequent interventional studies in patients with CAD and T2DM.