Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver
Night-time restricted feeding normalises clock genes and Pai-1 gene expression in the db/db mouse liver
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DOI：
10.1007/s00125-004-1461-0
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发表时间：
2004-08-01
期刊：
影响因子：
8.2
通讯作者：
Shibata, S
中科院分区：
文献类型：
--
作者：
Kudo, T;Akiyama, M;Shibata, S
目的/假设。派-1活性的增加被认为是心肌梗死的关键因素。小鼠派-1（m派-1）活性在体内表现出日节律，其转录似乎不仅受时钟基因控制，还受胰岛素和甘油三酯等体液因子控制。因此，我们研究了每日时钟基因和mPai-1 mRNA在db/db小鼠肝脏中的表达，这些小鼠表现出高水平的葡萄糖、胰岛素和糖皮质激素。使用红外检测系统测量自发活动。应用RT-PCR或原位杂交方法测量基因表达。使用测量试剂盒测量体液因子。db/db小鼠表现出减弱的自发活动节律。db/db小鼠肝脏中mPer 2 mRNA的节律性表达严重减少，mBmal 1振荡的相位提前，而mPai-1 mRNA高度组成性表达。夜间限制喂养导致恢复不仅从减少的运动活动，但也从减少Per 2和先进的mBmal 1 mRNA的节奏。db/db小鼠中mPai-1 mRNA的表达降低至远低于正常的水平。吡格列酮治疗使血糖和胰岛素水平轻微恢复正常，mPai-1基因表达轻微降低。我们证明了2型糖尿病损害了外周振荡器的振荡。夜间限制喂养而不是吡格列酮注射导致从减少的运动活动中恢复，并改变外周时钟和mPai-1 mRNA节律的振荡。因此，我们得出结论，计划限制食物摄入量可能是治疗糖尿病的一种有用的形式。
Aims/hypothesis. An increase in PAI-1 activity is thought to be a key factor underlying myocardial infarction. Mouse Pai-1 (mPai-1) activity shows a daily rhythm in vivo, and its transcription seems to be controlled not only by clock genes but also by humoral factors such as insulin and triglycerides. Thus, we investigated daily clock genes and mPai-1 mRNA expression in the liver of db/db mice exhibiting high levels of glucose, insulin and triglycerides.Methods. Locomotor activity was measured using an infrared detection system. RT-PCR or in situ hybridisation methods were applied to measure gene expression. Humoral factors were measured using measurement kits.Results. The db/db mice showed attenuated locomotor activity rhythms. The rhythmic expression of mPer2 mRNA was severely diminished and the phase of mBmal1 oscillation was advanced in the db/db mouse liver, whereas mPai-1 mRNA was highly and constitutively expressed. Night-time restricted feeding led to a recovery not only from the diminished locomotor activity, but also from the diminished Per2 and advanced mBmal1 mRNA rhythms. Expression of mPai-1 mRNA in db/db mice was reduced to levels far below normal. Pioglitazone treatment slightly normalised glucose and insulin levels, with a slight reduction in mPai-1 gene expression.Conclusions/interpretation. We demonstrated that Type 2 diabetes impairs the oscillation of the peripheral oscillator. Night-time restricted feeding rather than pioglitazone injection led to a recovery from the diminished locomotor activity, and altered oscillation of the peripheral clock and mPai-1 mRNA rhythm. Thus, we conclude that scheduled restricted food intake may be a useful form of treatment for diabetes.