Carvas João M, Vukolic Ana, Yepuri Gautham, Xiong Yuyan, Popp Katja, Schmutz Isabelle, Chappuis Sylvie, Albrecht Urs, Ming Xiu-Fen, Montani Jean-Pierre, Yang Zhihong
Faculty of Science, Division of Physiology, Department of Medicine, University of Fribourg Fribourg, Switzerland.
Front Physiol. 2012 Aug 23;3:337. doi: 10.3389/fphys.2012.00337. eCollection 2012.
Period2 (Per2) is an important component of the circadian clock. Mutation of this gene is associated with vascular endothelial dysfunction and altered glucose metabolism. The aim of this study is to further characterize whole body glucose homeostasis and endothelial nitric oxide (NO) production in response to insulin in the mPer2(Brdm1) mice. We show that mPer2(Brdm1) mice exhibit compromised insulin receptor activation and Akt signaling in various tissues including liver, fat, heart, and aortas with a tissue-specific heterogeneous diurnal pattern, and decreased insulin-stimulated NO release in the aortas in both active and inactive phases of the animals. As compared to wild type (WT) mice, the mPer2(Brdm1) mice reveal hyperinsulinemia, hypoglycemia with lower fasting hepatic glycogen content and glycogen synthase level, no difference in glucose tolerance and insulin tolerance. The mPer2(Brdm1) mice do not show increased predisposition to obesity either on normal chow or high fat diet compared to WT controls. Thus, mice with Per2 gene mutation show altered glucose homeostasis and compromised insulin-stimulated NO release, independently of obesity.
周期蛋白2（Per2）是生物钟的重要组成部分。该基因突变与血管内皮功能障碍和葡萄糖代谢改变有关。本研究的目的是进一步表征mPer2（Brdm1）小鼠对胰岛素反应时的全身葡萄糖稳态和内皮一氧化氮（NO）生成情况。我们发现，mPer2（Brdm1）小鼠在包括肝脏、脂肪、心脏和主动脉在内的各种组织中，胰岛素受体激活和Akt信号传导受损，呈现组织特异性的异质昼夜模式，并且在动物的活跃期和非活跃期，主动脉中胰岛素刺激的NO释放均减少。与野生型（WT）小鼠相比，mPer2（Brdm1）小鼠表现出高胰岛素血症、低血糖，空腹肝糖原含量和糖原合酶水平较低，葡萄糖耐量和胰岛素耐量无差异。与WT对照组相比，mPer2（Brdm1）小鼠在正常饮食或高脂饮食条件下均未表现出增加的肥胖易感性。因此，Per2基因突变的小鼠表现出葡萄糖稳态改变和胰岛素刺激的NO释放受损，且与肥胖无关。
