How does disruption of circadian rhythms induce diabetes?

越来越多的证据表明，昼夜节律紊乱会引发并放大代谢和心血管疾病。从事倒班工作的工人比例越来越高，而且在更广泛的人口中，这种节奏被破坏的频率越来越高，这意味着这种身体系统导致了肥胖和糖尿病以及相关疾病在我们社区和世界范围内日益流行。虽然我们现在开始了解我们的节律是如何与黑夜和白天同步的，但这种节律如何与我们的器官在正常和常见疾病状态下(如糖尿病)联系在一起，我们知之甚少。发现一组特殊的基因，称为时钟基因，在我们身体的所有细胞中发挥作用，并强烈影响我们肝脏、胰腺和心脏等器官的功能，这一发现尤为重要。我们假设环境(外源性)和遗传(内源性)引起的昼夜节律紊乱都会导致代谢功能障碍。这是由于中枢和外周时钟基因表达节律改变，进而改变新陈代谢节律，破坏葡萄糖动态平衡。本项目旨在确定节律性紊乱对新陈代谢的影响，特别强调节律性紊乱可能是糖尿病发生的诱因。

Increasing evidence suggests that disturbed circadian rhythms initiate and amplify metabolic and cardiovascular disease. The increasing and already high proportion of workers engaged in shiftwork, and increased frequency of disruption of these rhythms in the population more generally, implicate this body system as contributing to the growing epidemic of obesity and diabetes and related disorders in our community and world-wide. While we are now beginning to understand how our rhythms are synchronised to night and day, how this rhythmicity is linked to our organs in the normal and common disease states such as diabetes is poorly understood. The discovery of a special set of genes, called clock genes that function in all of the cells in our bodies and strongly influence the function of our organs such as the liver, pancreas and heart has been particularly important. We hypothesise that both environmentally (exogenous) and genetically (endogenous) induced disruption of circadian rhythms causes metabolic dysfunction. This is due to altered central and peripheral clock gene expression rhythms, which in turn alter metabolic rhythms and impair glucose homeostasis. This project aims to determine the impact of disrupted rhythmicity on metabolism with a particular emphasis on the possibility that the disrupted rhythmicity may be a predisposing factor for the development of diabetes.