Ding Wei, Chang Wen-Guang, Guo Xiao-Ci, Liu Ying, Xiao Dan-Dan, Ding Dan, Wang Jian-Xun, Zhang Xue-Juan
Department of General Medicine, The Affiliated Hospital, Qingdao University, Qingdao, China.
Center for Regenerative Medicine, Institute for Translational Medicine, Qingdao University, Qingdao, China.
Front Endocrinol (Lausanne). 2019 Apr 5;10:202. doi: 10.3389/fendo.2019.00202. eCollection 2019.
Cardiovascular disease is the major cause of death in patients with diabetes. Current treatment strategies for diabetes rely on lifestyle changes and glucose control to prevent angiopathy and organ failure. Exenatide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is used as an add-on therapy to insulin treatment. Exenatide also has multiple beneficial effects in addition to its hypoglycemic effects, such as preventing hepatic steatosis and protecting against cardiac injury from doxorubicin-induced cardiotoxicity or ischemic reperfusion. However, the mechanisms underlying the cardioprotective effects of exenatide in diabetes have not been fully clarified. To address this issue, we investigated the cardioprotective effects of exenatide in type 1 and type 2 diabetic mice. We found that exenatide simultaneously attenuated reactive oxidative species (ROS) production through increases in the antioxidant enzymes manganese dependent superoxide dismutase (MnSOD) and catalase. Moreover, exenatide decreased tumor protein P53 (p53) expression and prevented cell apoptosis in H9c2 cells. The presence of the catalase inhibitor 3-AT attenuated the effects of exenatide. Overall, the results strongly indicate that exenatide treatment may be protective against the development of diabetic cardiomyopathy.
心血管疾病是糖尿病患者的主要死因。目前糖尿病的治疗策略依赖于生活方式改变和血糖控制，以预防血管病变和器官衰竭。艾塞那肽是一种胰高血糖素样肽-1（GLP-1）受体激动剂，用作胰岛素治疗的附加疗法。艾塞那肽除了具有降血糖作用外，还具有多种有益作用，如预防肝脂肪变性以及保护心脏免受阿霉素诱导的心脏毒性或缺血再灌注损伤。然而，艾塞那肽在糖尿病中发挥心脏保护作用的机制尚未完全阐明。为了解决这个问题，我们研究了艾塞那肽对1型和2型糖尿病小鼠的心脏保护作用。我们发现，艾塞那肽通过增加抗氧化酶锰依赖性超氧化物歧化酶（MnSOD）和过氧化氢酶的含量，同时减弱活性氧（ROS）的产生。此外，艾塞那肽降低肿瘤蛋白P53（p53）的表达，并防止H9c2细胞发生细胞凋亡。过氧化氢酶抑制剂3-AT的存在减弱了艾塞那肽的作用。总体而言，结果有力地表明，艾塞那肽治疗可能对糖尿病性心肌病的发展具有保护作用。
