Consequences of exposure to light at night on the pancreatic islet circadian clock and function in rats.
Consequences of exposure to light at night on the pancreatic islet circadian clock and function in rats.
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DOI：
10.2337/db12-1543
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发表时间：
2013-10
期刊：
影响因子：
7.7
通讯作者：
Matveyenko AV
中科院分区：
文献类型：
--
作者：
Qian J;Block GD;Colwell CS;Matveyenko AV
昼夜节律紊乱、2型糖尿病(T2 DM)和胰岛衰竭之间存在相关性。然而，这种联系背后的机制在很大程度上是未知的。胰岛表达自我维持的生物钟，对于正常的β细胞功能和生存是必不可少的。我们假设，暴露在与人类昼夜节律紊乱和T2 DM易感性相关的环境条件下，会扰乱胰岛时钟和β细胞功能。为了解决这一假设，我们验证了使用PER-1：LUC转基因大鼠进行体外胰岛生物钟功能的连续纵向评估。利用这种方法，我们随后研究了夜间持续光照(LL)对大鼠胰岛生物钟和胰岛素分泌的影响。我们的数据表明，体内明暗周期的变化影响了胰岛时钟转录振荡的相位，而长期暴露于LL(10周)则通过损害时钟转录振荡的幅度、相位和胰岛间同步性来扰乱胰岛生物钟的功能。我们还报道，由于胰岛素分泌脉冲量的减少，暴露于LL会导致葡萄糖刺激的胰岛素分泌减少。我们的研究确定了现代生活中常见的昼夜节律紊乱可能导致T2 DM患者胰岛衰竭的潜在机制。
There is a correlation between circadian disruption, type 2 diabetes mellitus (T2DM), and islet failure. However, the mechanisms underlying this association are largely unknown. Pancreatic islets express self-sustained circadian clocks essential for proper β-cell function and survival. We hypothesized that exposure to environmental conditions associated with disruption of circadian rhythms and susceptibility to T2DM in humans disrupts islet clock and β-cell function. To address this hypothesis, we validated the use of Per-1:LUC transgenic rats for continuous longitudinal assessment of islet circadian clock function ex vivo. Using this methodology, we subsequently examined effects of the continuous exposure to light at night (LL) on islet circadian clock and insulin secretion in vitro in rat islets. Our data show that changes in the light–dark cycle in vivo entrain the phase of islet clock transcriptional oscillations, whereas prolonged exposure (10 weeks) to LL disrupts islet circadian clock function through impairment in the amplitude, phase, and interislet synchrony of clock transcriptional oscillations. We also report that exposure to LL leads to diminished glucose-stimulated insulin secretion due to a decrease in insulin secretory pulse mass. Our studies identify potential mechanisms by which disturbances in circadian rhythms common to modern life can predispose to islet failure in T2DM.
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影响因子：
9.2
作者：
Akhtar, RA;Reddy, AB;Kyriacou, CP
通讯作者：
Kyriacou, CP
影响因子：
7.7
作者：
Huang, Chang-jiang;Lin, Chia-yu;Butler, Peter C.
通讯作者：
Butler, Peter C.
影响因子：
10.5
作者：
Kondratov, Roman V.;Kondratova, Anna A.;Antoch, Marina P.
通讯作者：
Antoch, Marina P.
DOI：
10.1152/ajpendo.1996.271.2.e246
发表时间：
1996-08-01
影响因子：
5.1
作者：
Boden, G;Ruiz, J;Chen, XH
通讯作者：
Chen, XH
昼夜节律的代谢和能量学的融合。
DOI：
10.1126/science.1195027
发表时间：
2010-12-03
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bass J;Takahashi JS
通讯作者：
Takahashi JS