Loss of melatonin signalling and its impact on circadian rhythms in mouse organs regulating blood glucose
Loss of melatonin signalling and its impact on circadian rhythms in mouse organs regulating blood glucose
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DOI：
10.1016/j.ejphar.2009.01.029
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发表时间：
2009-03-15
影响因子：
5
通讯作者：
Peschke, Elmar
中科院分区：
文献类型：
--
作者：
Wuehlbauer, Eckhard;Gross, Elena;Peschke, Elmar
昼夜节律的传递是由结合特定生物钟因子的特定启动子序列介导的。松果体激素褪黑激素通过G蛋白偶联受体来同步这些由时钟产生的昼夜节律。这项研究的目的是阐明褪黑素作为胰腺和肝脏外周时钟的诱因的可能作用。逆转录聚合酶链式反应(RT-PCR)证实褪黑素受体MT1和MT2在小鼠胰腺、肝脏和下丘脑同时表达。对褪黑激素受体基因敲除小鼠胰腺和肝脏的时钟基因或时钟输出转录子PER1、DBP和混响α进行了分析，并检测了它们的相移和幅度变化。半定量Western印迹分析表明，在褪黑激素受体双基因敲除小鼠中，PER1蛋白的表达具有昼夜节律性，但幅度有所增加。此外，在基因敲除的动物中，观察到褪黑素受体缺陷对胰岛素转录的影响，以及胰岛素分泌和葡萄糖稳态调节的改变。与野生型相比，褪黑素受体MT1、MT2或MT(1)和MT2双敲除动物的胰岛胰岛素分泌增加。这些数据支持褪黑素与参与血糖调节的主要器官的功能同步，并对胰岛素的分泌起负面作用。(C)2009爱思唯尔B.V.保留所有权利。
The transmission of circadian rhythms is mediated by specific promoter sequences binding a particular circadian clock factor. The pineal hormone melatonin acts via G-protein-coupled receptors to synchronise these clock-generated circadian rhythms. The study was aimed to elucidate the possible role of melatonin as a zeitgeber for peripheral clocks in pancreas and liver. Reverse transcription polymerase chain reaction (RT-PCR) provided evidence of the simultaneous expression of the melatonin receptors MT1 and MT2 in mouse pancreas, liver and hypothalamus. Melatonin receptor knockout mice were analysed with respect to the clock gene- or clock-output transcripts PER1, DBP and RevErb alpha in pancreas and liver, and both the occurrence of phase shifts and amplitude changes were detected. Circadian PER1 protein expression was found to be retained in melatonin receptor double knockout mice with an increased amplitude as measured by semiquantitative Western blot analysis. Moreover, an impact of melatonin receptor deficiency on insulin transcripts, and altered regulation of insulin secretion and glucose homeostasis were monitored in the knockout animals. Insulin secretion from isolated islets of melatonin receptor MT1, MT2 or mT(1) and MT2 double melatonin receptor-knockout animals was found to be increased relative to the wild type These data support the idea that melatonin synchronises the functions of the major organs involved in blood glucose regulation and negatively acts on the insulin secretion. (C) 2009 Elsevier B.V. All rights reserved.