慢性间歇性低氧状态mTOR信号通路变化对大鼠胰岛β细胞数量的影响

目的通过慢性间歇性低氧(chronic intermittent hypoxia,CIH)大鼠模型,来探讨哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)信号通路变化对大鼠胰岛β细胞数量的影响。方法 18只成年雄性SD大鼠随机均分为常氧组(A组)、CIH组(B组)、药物CIH组(C组),BC组予CIH处理,C组给予腹腔注射雷帕霉素0.2mg/kg/day。5周后检测胰岛m TOR及通路相关蛋白指标e IF4E、p-S6的表达、每个胰岛胰岛素阳性区域的面积及胰岛β细胞数量,以及血清胰岛素含量。结果与A组相比,B组除e IF4E外各指标均升高,C组p-S6、每个胰岛内β细胞的个数及胰岛素阳性区域的面积减少。相对于B组,C组各指标均降低。结论 CIH状态下,m TOR信号通路激活诱导胰岛β细胞数量增多,雷帕霉素能抑制CIH引起的m TOR信号通路激活效应,降低m TOR通路相关蛋白指标表达水平和胰岛β细胞数量。

Sleep alterations in mammals:Did aquatic conditions inhibit rapid eye movement sleep?

Sleep has been studied widely in mammals and to some extent in other vertebrates. Higher vertebrates such as birds and mammals have evolved an inimitable rapid eye movement （REM） sleep state. During REM sleep, postural muscles become atonic and the temperature regulating machinery remains suspended. Although REM sleep is present in almost all the terrestrial mammals, the aquatic mammals have either radically reduced or completely eliminated REM sleep. Further, we found a significant negative correlation between REM sleep and the adaptation of the organism to live on land or in water. The amount of REM sleep is highest in terrestrial mammals, significantly reduced in semi-aquatic mammals and completely absent or negligible in aquatic mammals. The aquatic mammals are obligate swimmers and have to sur- face at regular intervals for air. Also, these animals live in thermally challenging environments, where the conductive heat loss is approximately -90 times greater than air. Therefore, they have to be moving most of the time. As an adaptation, they have evolved unihemispheric sleep, during which they can rove as well as rest. A condition that immobilizes muscle activity and suspends the thermoregulatory machinery, as happens during REM sleep, is not suitable for these animals. It is possible that, in accord with Darwin＇s theory, aquatic mammals might have abolished REM sleep with time. In this review, we discuss the possibility of the intrinsic role of aquatic conditions in the elimination of REM sleep in the aquatic mammals.

Chronic intermittent hypoxia increases β cell mass and activates the mammalian target of rapamycin/hypoxia inducible factor 1/vascular endothelial growth factor A pathway in mice pancreatic islet

Background Growing evidence from population and clinic based studies showed that obstructive sleep apnea （OSA） and its characterizing chronic intermittent hypoxia （IH） were independently associated with the development of type 2 diabetes mellitus.However,the pathogenesis by which OSA induces glucose metabolic disorders is not clear.We determined changes in pancreatic β cell mass and the mammalian target of rapamycin （mTOR）/hypoxia inducible factor 1 （HIF-1）/ vascular endothelial growth factor A （VEGF-A） pathway following IH exposure.Methods A controlled gas delivery system regulated the flow of nitrogen and oxygen into a customized cage housing mice during the experiment.Twenty-four male wild C57BL/6J mice were either exposed to IH （n=12） or intermittent air as a control （n=12） for 56 days.Mice were anaesthetized and sacrificed after exposure,pancreas samples were dissected for immunofluorescent staining.Insulin and DAPI staining labelled islet β cells.Insulin positive area and β cell number per islet were measured.P-S6,HIF-1α and VEGF-A staining were performed to detect the activation of mTOR/HIF-1NEGF-A pathway.Results After eight weeks of IH exposure,insulin positive area increased by an average of 18.5% （P 〈0.05）.The β cell number per islet increased （92 vs.55,respectively for IH and the control groups,P 〈0.05） with no change in the size of individual β cells.Islet expression of HIF-1α and VEGF-A were higher in IH group than control group,and percentage of p-S6 positive β cell also increased after IH exposure （16.8% vs.4.6% respectively for IH and the control groups,P 〈0.05）.Conclusion The number of pancreatic β cells increased as did the activity of the mTOR/HIF-1NEGF-A pathway after exposure to IH.