Kajimoto Jun, Matsumura Ritsuko, Node Koichi, Akashi Makoto
The Research Institute for Time Studies, Yamaguchi University, Yamaguchi, Japan.
Department of Cardiovascular Medicine, Saga University, Saga, Japan.
Genes Cells. 2018 May;23(5):393-399. doi: 10.1111/gtc.12582. Epub 2018 Apr 11.
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 ) 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.
哺乳动物的昼夜节律会通过光和食物等外部线索进行相位调整和放大。虽然经由中央生物钟视交叉上核的光输入途径已得到明确界定，但进食诱导的昼夜节律重置机制仍不明确，尤其是在人类中。动物研究表明，胰岛素作为一种在进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子。在本研究中，我们以拔取并培养的毛囊作为人类外周生物钟的代表，研究了胰岛素对生物钟基因表达昼夜特性的影响。我们的结果表明，胰岛素以相位响应的方式使离体培养毛囊的生物钟基因表达节律发生相位偏移或放大。为降低物种、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摘除的Period2::荧光素酶（Per2）小鼠的须毛囊，发现胰岛素对生物钟基因表达的影响是可重复的。这些结果提示了进食诱导的胰岛素重置人类外周昼夜生物钟的可能性。
