de Goede Paul, Foppen Ewout, Ritsema Wayne I G R, Korpel Nikita L, Yi Chun-Xia, Kalsbeek Andries
Laboratory of Endocrinology, Amsterdam University Medical Center, Amsterdam Gastroenterology & Metabolism, University of Amsterdam, Amsterdam, Netherlands.
Hypothalamic Integration Mechanisms Group, Netherlands Institute for Neuroscience (NIN), An Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, Netherlands.
Front Endocrinol (Lausanne). 2019 Aug 21;10:554. doi: 10.3389/fendo.2019.00554. eCollection 2019.
Epidemiological studies indicate that shift-workers have an increased risk of type 2 diabetes mellitus (T2DM). Glucose tolerance and insulin sensitivity both are dependent on the circadian timing system (i.e., the time-of-day) and fasting duration, in rodents as well as humans. Therefore, question is whether manipulation of the circadian timing system, for example by changing the timing of feeding and fasting, is a potential preventive treatment for T2DM. Time-restricted feeding (TRF) is well-known to have profound effects on various metabolic measures, including glucose metabolism. However, experiments that directly measure the effects of TRF on glucose tolerance and/or insulin sensitivity at different time points throughout the 24 h cycle are lacking. Here we show, in rats, that TRF in line with the circadian timing system (i.e., feeding during the active phase) improves glucose tolerance during intravenous glucose tolerance tests (ivGTT) in the active phase, as lower insulin levels were observed with similar levels of glucose clearance. However, this was not the case during the inactive phase in which more insulin was released but only a slightly faster glucose clearance was observed. Contrasting, TRF out of sync with the circadian timing system (i.e., feeding during the inactive phase) worsened glucose tolerance, although only marginally, likely because of adaptation to the 4 week TRF regimen. Our results show that TRF can improve glucose metabolism, but strict adherence to the time-restricted feeding period is necessary, as outside the regular eating hours glucose tolerance is worsened.
流行病学研究表明，轮班工作者患2型糖尿病（T2DM）的风险增加。在啮齿动物和人类中，葡萄糖耐量和胰岛素敏感性均依赖于昼夜节律系统（即一天中的时间）和禁食持续时间。因此，问题在于操纵昼夜节律系统，例如通过改变进食和禁食的时间，是否是T2DM的一种潜在预防治疗方法。限时进食（TRF）对包括葡萄糖代谢在内的各种代谢指标具有深远影响，这是众所周知的。然而，缺乏在整个24小时周期的不同时间点直接测量TRF对葡萄糖耐量和/或胰岛素敏感性影响的实验。在这里，我们在大鼠中表明，与昼夜节律系统一致的TRF（即在活跃期进食）在活跃期的静脉葡萄糖耐量试验（ivGTT）中改善了葡萄糖耐量，因为在葡萄糖清除水平相似的情况下观察到胰岛素水平较低。然而，在非活跃期并非如此，在该时期释放了更多的胰岛素，但仅观察到葡萄糖清除略有加快。相反，与昼夜节律系统不同步的TRF（即在非活跃期进食）使葡萄糖耐量恶化，尽管只是轻微恶化，这可能是由于对4周TRF方案的适应。我们的结果表明，TRF可以改善葡萄糖代谢，但必须严格遵守限时进食期，因为在正常进食时间之外葡萄糖耐量会恶化。
