Melatonin Signaling Controls the Daily Rhythm in Blood Glucose Levels Independent of Peripheral Clocks.
Melatonin Signaling Controls the Daily Rhythm in Blood Glucose Levels Independent of Peripheral Clocks.
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DOI：
10.1371/journal.pone.0148214
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Tosini G
中科院分区：
文献类型：
--
作者：
Owino S;Contreras-Alcantara S;Baba K;Tosini G
褪黑激素由松果体和视网膜以昼夜节律的方式有节奏地分泌，其合成高峰出现在夜间。一旦合成，褪黑激素通过结合两种特异性G蛋白偶联受体-褪黑激素受体1型（MT 1）和褪黑激素受体2型（MT 2）发挥其作用。最近的研究表明MT 1和MT 2参与了葡萄糖稳态的调节;然而，褪黑激素信号传递对葡萄糖代谢的时间线索的能力仍然知之甚少。在这里，我们报告说，在小鼠中的MT 1或MT 2的去除废除血糖水平的每日节律。有趣的是，去除褪黑激素受体对骨骼肌、肝脏和脂肪组织内时钟基因的节律表达模式产生了很小的影响。综上所述，我们的数据表明，在MT 1-/-和MT 2-/-小鼠中观察到的血糖日节律的丧失并不是胰岛素敏感组织内“中断”时钟的结果。最后，我们的研究结果强调了褪黑激素受体信号在血糖水平的日常调节中的昼夜贡献。
Melatonin is rhythmically secreted by both the pineal gland and retina in a circadian fashion, with its peak synthesis occurring during the night. Once synthesized, melatonin exerts its effects by binding to two specific G-protein coupled receptors–melatonin receptor type 1(MT1) and melatonin receptor type 2(MT2). Recent studies suggest the involvement of MT1 and MT2 in the regulation of glucose homeostasis; however the ability of melatonin signaling to impart timing cues on glucose metabolism remains poorly understood. Here we report that the removal of MT1 or MT2 in mice abolishes the daily rhythm in blood glucose levels. Interestingly, removal of melatonin receptors produced small effects on the rhythmic expression patterns of clock genes within skeletal muscle, liver, and adipose tissue. Taken together, our data suggest that the loss of the daily rhythm in blood glucose observed in MT1-/- and MT2-/- mice does not occur as a consequence of ‘disrupted’ clocks within insulin sensitive tissues. Finally our results highlight a diurnal contribution of melatonin receptor signaling in the daily regulation of blood glucose levels.