Oishi Katsutaka, Ohyama Sumika, Higo-Yamamoto Sayaka
Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Department of Applied Biological Science, Graduate School of Science and Technology, Tokyo University of Science, Noda, Chiba, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, Japan.
Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
Biochem Biophys Res Commun. 2018 Jan 22;495(4):2616-2621. doi: 10.1016/j.bbrc.2017.12.158. Epub 2017 Dec 28.
Sleep disturbances are associated with various metabolic diseases such as hypertension and diabetes. We had previously established a mouse model of a psychophysiological stress-induced chronic sleep disorder (CSD) characterized by disrupted circadian rhythms of wheel-running activity, core body temperature, and sleep-wake cycles. To evaluate the underlying mechanisms of metabolic disorders induced by CSD, we created mice with CSD for six weeks and fed them with a high-fat diet. Glucose intolerance with hyperglycemia resulted, although plasma insulin levels and body weight increases were identical between control and CSD mice. Gluconeogenesis and glycolysis were enhanced and suppressed, respectively, in the livers of CSD mice, because the mRNA expression of Pck1 was significantly increased, whereas that of Gck and Pklr were significantly decreased in the CSD mice. Adipose inflammation induced by the high-fat diet seemed suppressed by the CSD, because the mRNA expression levels of Adgre1, Ccl2, and Tnf were significantly downregulated in the adipose tissues of CSD mice. These findings suggest that CSD impair glucose tolerance by inducing gluconeogenesis and suppressing glycolysis. Hyperphasia with hypoleptinemia, hypercorticosteronemia, and increased plasma free fatty acids might be involved in the impaired glucose metabolism under a CSD. Further studies are needed to elucidate the endocrine and molecular mechanisms underlying the associations between sleep disorders and impaired glucose homeostasis that consequently causes diabetes.
睡眠障碍与多种代谢性疾病有关，如高血压和糖尿病。我们之前建立了一种心理生理应激诱导的慢性睡眠障碍（CSD）小鼠模型，其特征是轮转活动、核心体温和睡眠-觉醒周期的昼夜节律紊乱。为了评估CSD诱导的代谢紊乱的潜在机制，我们将小鼠诱导为CSD状态六周，并给它们喂食高脂饮食。尽管对照小鼠和CSD小鼠的血浆胰岛素水平和体重增加相同，但还是出现了伴有高血糖的葡萄糖不耐受。CSD小鼠肝脏中的糖异生增强，糖酵解受到抑制，因为Pck1的mRNA表达显著增加，而Gck和Pklr的mRNA表达在CSD小鼠中显著降低。高脂饮食诱导的脂肪炎症似乎被CSD抑制，因为CSD小鼠脂肪组织中Adgre1、Ccl2和Tnf的mRNA表达水平显著下调。这些发现表明，CSD通过诱导糖异生和抑制糖酵解损害葡萄糖耐量。食欲亢进伴低瘦素血症、高皮质酮血症和血浆游离脂肪酸增加可能与CSD状态下受损的葡萄糖代谢有关。需要进一步研究以阐明睡眠障碍与受损的葡萄糖稳态之间关联的内分泌和分子机制，而这种关联最终会导致糖尿病。
