Wu Tao, ZhuGe Fen, Zhu Yali, Wang Nan, Jiang Qianru, Fu Haoxuan, Li Yongjun, Fu Zhengwei
College of Biological and Environmental Engineering, Zhejiang University of Technology, No.6 District, Zhaohui, Hangzhou, Zhejiang, 310032, China.
J Physiol Biochem. 2014 Mar;70(1):61-71. doi: 10.1007/s13105-013-0281-4. Epub 2013 Aug 17.
The aim of this study was to investigate whether the entrainment of light cue is affected or not in diabetic animals. We found that the individual light/dark (LD) reversal showed a tissue- and gene-specific effect on the circadian phases of peripheral clock genes, which was generally similar between the control and diabetic rats. In the liver and heart, the peak phases of examined clock genes (Bmal1, Rev-erbα, Per1, and Per2) were slightly shifted by 0∼4 h in the liver and heart of control and diabetic rats. However, we found that the peak phases of these clock genes were greatly shifted by 8∼12 h after the LD reversal for 7 days in the pineal gland of both control and diabetic rats. However, the activity rhythm was greatly different between two groups. After the individual LD reversal, the activity rhythm was completely shifted in the control rats but retained in the diabetic rats. These observations suggested that the behavioral rhythm of diabetic rats may be uncoupled from the master clock after the individual LD reversal. Moreover, we also found that the serum glucose levels of diabetic rats kept equally high throughout the whole day without any shift of peak phase after the individual reversal of LD cycle. While the serum glucose levels of control rats were tightly controlled during the normal and LD reversal conditions. Thus, the impaired insulin secretion induced uncontrollable serum glucose level may result in uncoupled activity rhythm in the diabetic rats after the individual LD reversal.
本研究的目的是调查光信号的同步化在糖尿病动物中是否受到影响。我们发现,个体明暗(LD)颠倒对外周生物钟基因的昼夜节律相位呈现出组织和基因特异性效应,这在对照大鼠和糖尿病大鼠之间总体相似。在肝脏和心脏中,对照大鼠和糖尿病大鼠肝脏与心脏中检测的生物钟基因(Bmal1、Rev-erbα、Per1和Per2)的峰值相位略有偏移0至4小时。然而,我们发现,在对照大鼠和糖尿病大鼠的松果体中,经过7天的LD颠倒后,这些生物钟基因的峰值相位大幅偏移了8至12小时。然而,两组之间的活动节律有很大差异。个体LD颠倒后,对照大鼠的活动节律完全改变,而糖尿病大鼠的活动节律则保持不变。这些观察结果表明,个体LD颠倒后,糖尿病大鼠的行为节律可能与主生物钟解耦。此外,我们还发现,糖尿病大鼠的血清葡萄糖水平在一整天内都保持同样高,在个体颠倒LD周期后峰值相位没有任何变化。而对照大鼠的血清葡萄糖水平在正常和LD颠倒条件下都受到严格控制。因此,胰岛素分泌受损导致血清葡萄糖水平无法控制,可能导致个体LD颠倒后糖尿病大鼠的活动节律解耦。