Liraglutide Activates AMPK Signaling and Partially Restores Normal Circadian Rhythm and Insulin Secretion in Pancreatic Islets in Diabetic Mice
Liraglutide Activates AMPK Signaling and Partially Restores Normal Circadian Rhythm and Insulin Secretion in Pancreatic Islets in Diabetic Mice
复制标题
Liraglutide 激活 AMPK 信号传导并部分恢复糖尿病小鼠胰岛的正常昼夜节律和胰岛素分泌。
DOI：
10.1248/bpb.b15-00024
复制
发表时间：
2015-08-01
影响因子：
2
通讯作者：
Chen, Li
中科院分区：
文献类型：
--
作者：
Wang, Kexin;Sun, Yu;Chen, Li
胰岛β细胞功能不全在糖尿病的发生发展中起着重要作用。环境因素，包括生活方式，在β细胞功能障碍中起着关键作用。现代生活方式影响着中枢和外周器官固有的生物钟。最近的研究表明，胰岛正常的内在生物钟对于胰岛细胞的生存和胰岛素分泌功能是必不可少的。然而，总体而言，这些数据并不确定。我们的研究表明，链脲佐菌素诱导的1型糖尿病小鼠胰岛昼夜节律的紊乱可能与β细胞功能受损和葡萄糖耐量异常有关。利拉鲁肽是一种胰高血糖素样肽-1(GLP-1)类似物，可以部分恢复正常的昼夜节律，激活5‘AMP激活的蛋白激酶(AMPK)信号通路。我们的研究提供了证据表明，利拉鲁肽可以通过减轻胰岛固有昼夜节律的破坏和激活AMPK信号来恢复小鼠模型的β细胞功能，防止糖尿病的发展。
beta-Cell insufficiency plays an important role in the development of diabetes. Environmental factors, including lifestyle, play a critical role in beta-cell dysfunction. Modern lifestyles affect the inherent circadian clock in central and peripheral organs. Recent studies have demonstrated that the normal intrinsic circadian clock in islets was essential for the viability of beta cells and their insulin secretory function. Overall, however, the data are inconclusive. Our study demonstrated that the disrupted circadian rhythm of islets in streptozotocin induced type1 diabetic mice may be associated with impaired beta-cell function and glucose intolerance. Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, could partially restore the normal circadian rhythm and activate the 5' AMP-activated protein kinase (AMPK) signaling pathway. Our study provided evidence demonstrating that Liraglutide might restore beta-cell function and protect against the development of diabetes in a mouse model by attenuating the disruption of the intrinsic circadian rhythm in islets and by activating AMPK signaling.