BACKGROUND Glucagon-like peptide-1 (GLP-1) reduces cardiovascular events in diabetic patients; however, its counter-protective effects have also been suggested in patients with heart failure and the clear explanation for its mechanisms have not yet been offered. METHODS The effects of GLP-1 analog on cardiac function and energy metabolism, especially glycemic and lipid metabolisms were elucidated using non-diabetic J2N-k hamsters which showed spontaneous dilated cardiomyopathy. J2N-k hamsters were treated with PBS (HF group), low-dose (HF-L group) or high-dose liraglutide (HF-H group). RESULTS In failing heart, GLP-1 analog exerted further deteriorated cardiac function (e.g. positive and negative dP/dt; p = 0.01 and p = 0.002, respectively) with overt fibrosis and cardiac enlargement (heart/body weight, 5.7 ± 0.2 in HF group versus 7.6 ± 0.2 in HF-H group; p = 0.02). The protein expression of cardiac muscles indicated the energy starvation status. Indirect calorimetry showed that failing hearts consumed higher energy and carbohydrate than normal hearts; moreover, this tendency was augmented by GLP-1 analog administration. Upon 10% glucose solution loading with GLP-1 analog administration (HF-H-G group) as complementary experiments, the cardiac function and fibrosis significantly ameliorated, whereas carbohydrate utilization augmented further and lipid utilization reduced more. The prognosis of HF-H-G group also significantly improved (p = 0.025). CONCLUSIONS Glucagon-like peptide-1 analog caused the relative but desperate shortage of glycemic energy source for the failing cardiac muscles and it may restrict ATP synthesis, resulting in cardiac function deterioration. Therefore, appropriate energy supply and amount of carbohydrate intake should be carefully considered when administrating incretin-related drugs to patients with heart failure.

中文翻译：

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GLP-1类似物利拉鲁肽在非糖尿病性扩张型心肌病患者心力衰竭中由于精力不足引起的心脏功能障碍。

背景技术胰高血糖素样肽1（GLP-1）可以减少糖尿病患者的心血管事件。然而，在心力衰竭患者中也有人提出了它的反保护作用，并且尚未对其机理进行明确的解释。方法使用自发性扩张型心肌病的非糖尿病J2N-k仓鼠阐明GLP-1类似物对心脏功能和能量代谢的影响，尤其是血糖和脂质代谢。用PBS（HF组），低剂量（HF-L组）或高剂量利拉鲁肽（HF-H组）处理J2N-k仓鼠。结果在心脏衰竭时，GLP-1类似物的心脏功能进一步恶化（例如，阳性和阴性dP / dt；分别为p = 0.01和p = 0.002），并伴有明显的纤维化和心脏肿大（心脏/体重，HF为5.7±0.2）组与7.6±0。HF-H组2个；p = 0.02）。心肌的蛋白质表达表明能量缺乏状态。间接量热法显示，衰竭的心脏比正常的心脏消耗更多的能量和碳水化合物。此外，这种趋势通过GLP-1类似物的给药而增强。在补充了GLP-1类似物（HF-HG组）的10％葡萄糖溶液负荷下，心功能和纤维化明显改善，而碳水化合物的利用进一步增加，脂质的利用进一步降低。HF-HG组的预后也明显改善（p = 0.025）。结论胰高血糖素样肽1类似物引起了衰竭心肌的相对但迫切的血糖能量短缺，并且它可能限制ATP的合成，从而导致心脏功能恶化。所以，