Liraglutide relieves myocardial damage by promoting autophagy via AMPK-mTOR signaling pathway in zucker diabetic fatty rat
Liraglutide relieves myocardial damage by promoting autophagy via AMPK-mTOR signaling pathway in zucker diabetic fatty rat
复制标题
利拉鲁肽通过AMPK-mTOR信号通路促进自噬减轻zucker糖尿病脂肪大鼠心肌损伤
DOI：
10.1016/j.mce.2017.03.029
复制
发表时间：
2017
影响因子：
4.1
通讯作者：
Wang Xianbao
中科院分区：
文献类型：
--
作者：
Zhang Ya;Ling Yuanna;Yang Li;Cheng Yanzhen;Yang Pingzhen;Song Xudong;Tang Huixiong;Zhong Yongkang;Tang Lu;He Shangfei;Yang Shuangli;Chen Aihua;Wang Xianbao
利拉鲁肽是一种用于治疗2型糖尿病的降糖药，据报道，在临床试验和动物实验中可发挥心脏保护作用。然而，利拉鲁肽对糖尿病心肌病的心脏保护机制尚未得到充分说明。本研究旨在研究利拉鲁肽是否通过促进自噬减轻糖尿病心肌损伤及其潜在机制。我们的研究结果表明，利拉鲁肽显著降低肌酸激酶（CK）和乳酸脱氢酶（LDH）的水平，改善左心室功能状态，减轻心肌纤维化的Zucker糖尿病脂肪（ZDF）大鼠模型。利拉鲁肽还减轻了NRC中高葡萄糖诱导的损伤。自噬抑制剂氯喹（CQ）可部分逆转上述作用。利拉鲁肽在体内和体外模型中促进心肌自噬。此外，利拉鲁肽诱导的自噬增强与AMPK磷酸化增加和mTOR磷酸化减少有关，其被AMPK抑制剂化合物C（Comp C）部分消除。总的来说，我们的数据提供了利拉鲁肽通过促进AMPK依赖性自噬介导糖尿病心肌损伤的证据。
Liraglutide, a glucose-lowering agent used to treat type 2 diabetic mellitus is reported to exert cardioprotective effects in clinical trials and animal experiments. However, the cardioprotective mechanism of liraglutide on diabetic cardiomyopathy has not been fully illustrated. The present study was performed to investigate whether liraglutide alleviates diabetic myocardium injury by promoting autophagy and its underlying mechanisms. Our results show that liraglutide significantly reduced the levels of creatine kinase (CK) and lactate dehydrogenase (LDH), improved left ventricular functional status and alleviated myocardial fibrosis in the Zucker diabetic fatty (ZDF) rat model. Liraglutide also mitigated high glucose-induced injury in NRCs. However these effects were partly reversed by the autophagic inhibitor chloroquine (CQ). Liraglutide promoted myocardial autophagy in the vivo and in the vitro models. Furthermore, liraglutide-induced enhancement of autophagy was related to increased AMPK phosphorylation and decreased mTOR phosphorylation, which was partially abolished by the AMPK inhibitor compound C (Comp C). Collectively, our data provide evidence that liraglutide mediated diabetic myocardium injury by promoting AMPK-dependent autophagy.