Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy
Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy
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DOI：
10.1161/01.cir.0000139339.85840.dd
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发表时间：
2004-08-24
期刊：
影响因子：
37.8
通讯作者：
Shannon, RP
中科院分区：
文献类型：
--
作者：
Nikolaidis, LA;Elahi, D;Shannon, RP
背景-衰竭的心脏表现出对葡萄糖作为其代谢底物的偏好。增强心肌葡萄糖摄取是否对心力衰竭患者左心室收缩功能有积极影响仍不确定。胰高血糖素样肽-1（GLP-1）是一种天然存在的肠促胰岛素，具有强效促胰岛素作用，当葡萄糖水平降至4 mmol以下时，其作用减弱。我们研究了重组GLP-1（rGLP-1）对LV和全身血流动力学和心肌基质摄取的影响，在清醒的狗与先进的扩张型心肌病（DCM）作为一种机制，克服心肌胰岛素抵抗和增强心肌葡萄糖uptake.Methods和Results -35只狗进行了仪器和研究在完全清醒的状态。通过28天的快速起搏诱导晚期DCM。16只患有晚期DCM的狗接受rGLP-1（1.5 pmol . kg（-1）。min（-1））。8只DCM犬作为对照，接受48小时盐水输注（3 mL/d）。输注rGLP-1与LV dP/dt（98%）、每搏输出量（102%）和心输出量（57%）显著增加（P < 0.02）以及LV舒张末期压、心率和全身血管阻力显著降低相关。rGLP-1增加心肌胰岛素敏感性和心肌葡萄糖摄取。在盐水对照组中没有显著变化。结论- rGLP-1显着改善左心室和全身血流动力学在清醒的狗与先进的DCM诱导快速起搏。rGLP-1具有拟胰岛素和胰高血糖素抑制特性，导致心肌葡萄糖摄取增加。rGLP-1在失代偿性心力衰竭中可能是一种有用的代谢辅助剂。
Background - The failing heart demonstrates a preference for glucose as its metabolic substrate. Whether enhancing myocardial glucose uptake favorably influences left ventricular (LV) contractile performance in heart failure remains uncertain. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with potent insulinotropic effects the action of which is attenuated when glucose levels fall below 4 mmol. We examined the impact of recombinant GLP-1 (rGLP-1) on LV and systemic hemodynamics and myocardial substrate uptake in conscious dogs with advanced dilated cardiomyopathy (DCM) as a mechanism for overcoming myocardial insulin resistance and enhancing myocardial glucose uptake.Methods and Results - Thirty-five dogs were instrumented and studied in the fully conscious state. Advanced DCM was induced by 28 days of rapid pacing. Sixteen dogs with advanced DCM received a 48-hour infusion of rGLP-1 (1.5 pmol . kg(-1) . min(-1)). Eight dogs with DCM served as controls and received 48 hours of a saline infusion (3 mL/d). Infusion of rGLP-1 was associated with significant ( P < 0.02) increases in LV dP/dt (98%), stroke volume (102%), and cardiac output (57%) and significant decreases in LV end-diastolic pressure, heart rate, and systemic vascular resistance. rGLP-1 increased myocardial insulin sensitivity and myocardial glucose uptake. There were no significant changes in the saline control group.Conclusions - rGLP-1 dramatically improved LV and systemic hemodynamics in conscious dogs with advanced DCM induced by rapid pacing. rGLP-1 has insulinomimetic and glucagonostatic properties, with resultant increases in myocardial glucose uptake. rGLP-1 may be a useful metabolic adjuvant in decompensated heart failure.