Untimely oxidative stress in β-cells leads to diabetes - Role of circadian clock in β-cell function.
Untimely oxidative stress in β-cells leads to diabetes - Role of circadian clock in β-cell function.
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DOI：
10.1016/j.freeradbiomed.2018.02.022
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发表时间：
2018-05-01
影响因子：
7.4
通讯作者：
Yechoor V
中科院分区：
文献类型：
--
作者：
Lee J;Ma K;Moulik M;Yechoor V
糖尿病是由于 β 细胞功能丧失所致。随着全球糖尿病患者数量达到流行病的程度，了解导致糖尿病患病率不断上升的机制至关重要。其中一个因素就是昼夜节律紊乱，轮班工作、光污染、时差、屏幕时间增加，所有这些都是潜在的促成因素。尽管几十年来，昼夜节律紊乱在流行病学上一直与糖尿病和其他代谢紊乱相关，但直到最近，人们才对潜在的分子机制有了更好的了解。通过使用基因删除小鼠模型操纵环境或遗传因素来扰乱昼夜节律，已经证明了昼夜节律在全身代谢中的重要性。核心时钟基因（特别是小鼠β细胞中的核心时钟基因）的遗传破坏现在已经证明了内在β细胞时钟在调节功能中的重要性。最近的工作还显示了生物钟和β细胞中增强子的相互作用，表明生物钟对转录和细胞功能的高度整合调节。整个身体或仅 β 细胞时钟的破坏会导致线粒体功能显着受损、解偶联、囊泡运输受损、β 细胞氧化应激，最终导致葡萄糖刺激的胰岛素分泌受损和糖尿病。在这篇综述中，我们探讨了生物钟在减轻氧化应激和保护 β 细胞功能中的作用。
Diabetes results from a loss of β-cell function. With the number of people with diabetes reaching epidemic proportions globally, understanding mechanisms that are contributing to this increasing prevalence is critical. One such factor has been circadian disruption, with shift-work, light pollution, jet-lag, increased screen time, all acting as potential contributory factors. Though circadian disruption has been epidemiologically associated with diabetes and other metabolic disorders for many decades, it is only recently that there has been a better understanding of the underlying molecular mechanisms. Experimental circadian disruption, via manipulation of environmental or genetic factors using gene-deletion mouse models, has demonstrated the importance of circadian rhythms in whole body metabolism. Genetic disruption of core clock genes, specifically in the β-cells in mice, have, now demonstrated the importance of the intrinsic β-cell clock in regulating function. Recent work has also shown the interaction of the circadian clock and enhancers in β-cells, indicating a highly integrated regulation of transcription and cellular function by the circadian clock. Disruption of either the whole body or only the β-cell clock leads to significant impairment of mitochondrial function, uncoupling, impaired vesicular transport, oxidative stress in β-cells and finally impaired glucose-stimulated insulin secretion and diabetes. In this review, we explore the role of the circadian clock in mitigating oxidative stress and preserving β-cell function.
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DOI：
10.1126/science.1198125
发表时间：
2011-03-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Feng D;Liu T;Sun Z;Bugge A;Mullican SE;Alenghat T;Liu XS;Lazar MA
通讯作者：
Lazar MA
影响因子：
4.1
作者：
Allaman-Pillet, N;Roduit, R;Bonny, C
通讯作者：
Bonny, 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.
新的遗传基因座涉及禁食葡萄糖稳态及其对2型糖尿病风险的影响。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
29
作者：
Grimaldi B;Bellet MM;Katada S;Astarita G;Hirayama J;Amin RH;Granneman JG;Piomelli D;Leff T;Sassone-Corsi P
通讯作者：
Sassone-Corsi P