Cell-autonomous circadian clocks exist in nearly every organ and function to maintain homeostasis through a complex series of transcriptional-translational feedback loops. The response of these peripheral clocks to external perturbations, such as chronic jetlag and shiftwork, has been extensively investigated. However, an evaluation of the effects of chronic jetlag on the mouse pancreatic transcriptome is still lacking. Herein we report an evaluation of the diurnal variations encountered in the pancreatic transcriptome following exposure to an established chronic jetlag protocol. We found approximately 5.4% of the pancreatic transcriptome was rhythmic. Following chronic jetlag, we found the number of rhythmic transcripts decreased to approximately 3.6% of the transcriptome. Analysis of the core clock genes, which orchestrate circadian physiology, revealed that nearly all exhibited a shift in the timing of peak gene expression - known as a phase shift. Similarly, over 95% of the rhythmically expressed genes in the pancreatic transcriptome exhibited a phase shift, many of which were found to be important for metabolism. Evaluation of the genes involved in pancreatic exocrine secretion and insulin signaling revealed many pancreas-specific genes were also rhythmically expressed and several displayed a concomitant phase shift with chronic jetlag. Phase differences were found 9 days after normalization, indicating a persistent failure to reentrain to the new light-dark cycle. This study is the first to evaluate the endogenous pancreatic clock and rhythmic gene expression in whole pancreas over 48 hours, and how the external perturbation of chronic jetlag affects the rhythmic expression of genes in the pancreatic

中文翻译：

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慢性时差引起的胰腺昼夜基因表达的改变


细胞自主生物钟存在于几乎每个器官中，并通过一系列复杂的转录翻译反馈回路维持体内平衡。这些外围时钟对外部扰动（例如慢性时差和轮班工作）的响应已被广泛研究。然而，仍缺乏对慢性时差对小鼠胰腺转录组影响的评估。在此，我们报告了在暴露于已建立的慢性时差方案后胰腺转录组中遇到的昼夜变化的评估。我们发现大约 5.4% 的胰腺转录组是有节律的。慢性时差反应后，我们发现节律转录本的数量减少至转录组的约 3.6%。对协调昼夜节律生理学的核心时钟基因的分析表明，几乎所有基因都表现出峰值基因表达时间的变化 - 称为相移。同样，胰腺转录组中超过 95% 的节律表达基因表现出相移，其中许多基因被发现对新陈代谢很重要。对涉及胰腺外分泌分泌和胰岛素信号传导的基因的评估显示，许多胰腺特异性基因也有节奏地表达，并且一些基因表现出与慢性时差相伴的相移。标准化后 9 天发现相位差异，表明重新进入新的光暗循环持续失败。这项研究首次评估了48小时内整个胰腺的内源性胰腺时钟和节律性基因表达，以及慢性时差的外部扰动如何影响胰腺中基因的节律性表达