Lee Ihn Suk, Park Ki Cheol, Yang Keum-Jin, Choi Hyunsu, Jang Yi Sun, Lee Jong Min, Kim Hye Soo
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Clinical Research Institute, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea.
Obes Res Clin Pract. 2016 May-Jun;10(3):315-26. doi: 10.1016/j.orcp.2015.07.011. Epub 2015 Aug 24.
Exenatide has beneficial effects on insulin sensitivity in several animal models; however, its mechanism of action remains unclear. Furthermore, the relationship between the effect of exenatide on the changes in the relative abundance of microRNAs (miRNAs), which play a role in regulating glucose and lipid metabolism, is not fully understood. Therefore, we assessed the effect of exenatide on miRNA expression in a high-fat diet (HFD)-induced mouse model of obesity. Both HFD control and exenatide-treated HFD mice showed similar body weight gain and increase in β-cell mass. Insulin levels were significantly lower in exenatide-treated mice than in HFD control mice. The levels of miRNA-15a, 29c, 124a, and 375 in the pancreas were significantly increased in HFD control mice. Furthermore, the levels of miRNA-29c, 124a, and 146a in the liver and miRNA-15a, 29c, 124a, and 146a in the muscle were significantly increased. In contrast, the levels of miRNA-15a, 29c, 124a, and 375 in the serum were significantly decreased. These effects were reversed by treatment with exenatide. Our results provide experimental evidence that exenatide-mediated amelioration of insulin sensitivity is associated with antagonistic changes in the relative abundance of miRNA-15a, 29c, 124a, and 375 in tissues and serum, thus highlighting their usefulness as biomarkers for monitoring insulin sensitivity and response to exenatide treatment in experimental diabetes.
艾塞那肽在多种动物模型中对胰岛素敏感性具有有益作用；然而，其作用机制仍不清楚。此外，艾塞那肽对在调节葡萄糖和脂质代谢中起作用的微小RNA（miRNA）相对丰度变化的影响之间的关系尚未完全了解。因此，我们评估了艾塞那肽对高脂饮食（HFD）诱导的肥胖小鼠模型中miRNA表达的影响。HFD对照组和艾塞那肽治疗的HFD小鼠体重增加和β细胞量增加情况相似。艾塞那肽治疗的小鼠胰岛素水平显著低于HFD对照组小鼠。HFD对照组小鼠胰腺中miRNA-15a、29c、124a和375的水平显著升高。此外，肝脏中miRNA-29c、124a和146a以及肌肉中miRNA-15a、29c、124a和146a的水平显著升高。相比之下，血清中miRNA-15a、29c、124a和375的水平显著降低。这些作用通过艾塞那肽治疗得以逆转。我们的结果提供了实验证据，表明艾塞那肽介导的胰岛素敏感性改善与组织和血清中miRNA-15a、29c、124a和375相对丰度的拮抗变化有关，从而突出了它们作为监测实验性糖尿病中胰岛素敏感性和对艾塞那肽治疗反应的生物标志物的有用性。
