Potential role of the pancreatic hormone insulin in resetting human peripheral clocks
Potential role of the pancreatic hormone insulin in resetting human peripheral clocks
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DOI：
10.1111/gtc.12582
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发表时间：
2018-05-01
期刊：
影响因子：
2.1
通讯作者：
Akashi, Makoto
中科院分区：
文献类型：
--
作者：
Kajimoto, Jun;Matsumura, Ritsuko;Akashi, Makoto
哺乳动物的昼夜节律是由光和食物等外部信号进行相位调整和放大的。虽然通过中央时钟-视交叉上核的光输入通路已经被很好地定义，但摄食诱导的昼夜节律重置的机制仍然不清楚，特别是在人类中。动物研究表明，胰岛素是一种在摄食后迅速分泌的胰腺激素，是肝脏和脂肪组织等一些外周生物钟的输入因素。在这项研究中，以拔除和培养的毛囊为代表的人类外周时钟，我们研究了胰岛素对时钟基因表达的昼夜节律特征的影响。我们的结果表明，胰岛素以一种相位响应的方式移位或放大体外培养毛囊的时钟基因表达节律。为了减少物种、遗传或环境背景以及实验方法的差异影响实验结果的可能性，我们还用胰岛素处理了手术提取的Perod2：：荧光素酶(PER2(Luc))小鼠的胡须毛囊，发现胰岛素对时钟基因表达的影响是可重现的。这些结果表明，喂食诱导的胰岛素可能会重置人类的外周生物钟。
Mammalian circadian rhythms are phase-adjusted and amplified by external cues such as light and food. While the light input pathway via the central clock, the suprachiasmatic nucleus, has been well defined, the mechanism of feeding-induced circadian resetting remains undefined, particularly in humans. Animal studies have indicated that insulin, a pancreatic hormone that is secreted rapidly in response to feeding, is an input factor for a few peripheral clocks, such as liver and adipose tissue. In this study, using plucked and cultured hair follicles as a representative human peripheral clock, we examined the effect of insulin on circadian characteristics of clock gene expression. Our results demonstrate that insulin phase-shifts or amplifies the clock gene expression rhythms of ex vivo cultured hair follicles in a phase-responsive manner. To reduce the possibility that differences in species, genetic or environmental background, and experimental methods affected experimental outcomes, we also treated surgically extracted whisker follicles of Period2::Luciferase (Per2(Luc)) mice with insulin and found that the effect of insulin on clock gene expression was reproducible. These results suggest the possibility that feeding-induced insulin resets peripheral circadian clocks in humans.