Exenatide Protects Against Cardiac Dysfunction by Attenuating Oxidative Stress in the Diabetic Mouse Heart
Exenatide Protects Against Cardiac Dysfunction by Attenuating Oxidative Stress in the Diabetic Mouse Heart
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DOI：
10.3389/fendo.2019.00202
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发表时间：
2019-04-05
影响因子：
5.2
通讯作者：
Zhang, Xue-juan
中科院分区：
文献类型：
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作者：
Ding, Wei;Chang, Wen-guang;Zhang, Xue-juan
心血管疾病是糖尿病患者死亡的主要原因。目前糖尿病的治疗策略依赖于生活方式的改变和血糖控制，以防止血管病和器官衰竭。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治疗。艾塞那肽除具有降血糖作用外，还具有多种有益作用，如预防肝脂肪变性和防止多柔比星诱导的心脏毒性或缺血再灌注引起的心脏损伤。然而，艾塞那肽在糖尿病中的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在1型和2型糖尿病小鼠中的心脏保护作用。我们发现，exenetrin同时衰减活性氧化物质（ROS）的生产，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。此外，exenlavine降低肿瘤蛋白P53（p53）的表达，并阻止细胞凋亡的H9 c2细胞。过氧化氢酶抑制剂3-AT的存在减弱了exenetrine的作用。总体而言，结果强烈表明，exenlavine治疗可能对糖尿病心肌病的发展具有保护作用。
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.