GAS6/AXL信号通路失活对小鼠能量代谢的影响  

Effect of GAS6/AXL signaling pathway inactivation on energy metabolism in mice

作　　者：高娟[1] 郭萌[1] 霍学云[1] 李振坤[1] 张双悦[1] 杜小燕[1] 王超[1] 陈振文[1] 王钜[1] 

机构地区：[1]首都医科大学基础医学院,北京100069

出　　处：《中国实验动物学报》2014年第1期57-62,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金项目(No.31272393);首都医科大学基础临床合作项目(No.13JL32)

摘　　要：目的研究小鼠生长停滞特异蛋白6(growth arrest-specific gene 6,GAS6)信号通路的失活对维持机体能量代谢稳态的影响。方法以GAS6主要受体Axl基因敲除(Axl-/-)小鼠及其野生型(Axl+/+)小鼠为研究对象,比较两组动物基础血糖值、血脂四项指标、脂肪系数及骨骼肌中糖代谢信号蛋白PI3K、AKT与葡萄糖转运蛋白4(glucose transporter 4,GLUT4)基因表达水平及其蛋白磷酸化水平间的差异;同时检测人工诱发2型糖尿病(type2 diabetes mellitus,T2DM)造模前后小鼠血清GAS6蛋白水平与T2DM模型成模率的改变之间是否存在相关性。结果 Axl-/-小鼠血脂出现异常波动,且脂肪沉积率显著高于野生型小鼠(P<0.01)。Axl-/-小鼠血糖调节能力受损,其空腹血糖值显著高于野生型,骨骼肌Glut4的mRNA水平升高,而PI3K、AKT和GLUT4蛋白的磷酸化水平均略有下降。经人工诱发T2DM后,Axl+/+和Axl-/-小鼠血浆中GAS6浓度均显著低于各自对照组,且Axl-/-小鼠T2DM模型的成模率是Axl+/+小鼠的2倍(P<0.01)。结论 GAS6/AXL信号通路的激活在一定程度上降低血糖和抑制脂肪沉积。Objective To investigate the effects of growth arrest-specific gene 6 （GAS6） inactivation on maintaining mouse energy metabolic homeostasis. Methods Axl gene encodes the major receptor of Gas6. Wild type gene （Axl＋/＋） and Axl gene-deficient （Axl-/-） mice were used as research models. For each genotype mice, the fasting glucose, blood lipids, aliphatic index in the blood, and the mRNA expression and protein phosphorylation levels of PI3K, AKT and glucose transporter 4 （GLUT4） in skeletal muscle were determined. After high fat high cholesterol diet-induced type 2 diabetes mellitus （T2DM） models from the two genotype mice were generated, the plasma Gas6 concentrations of the mice were detected respectively so as to compare the effect of Axl deficiency on the success ratio of induced T2DM models. Results Abnormal blood lipids in Axl-/- mice were observed, and the fat deposition rate was significantly higher than that of the wild-type mice as well （P〈0.01）. The stability of blood glucose in Axl-/- mice was impaired, in which the fasting glucose level in Axl-/- mice was significantly higher than that in the wild-type mice, and the mRNA level of Glut4 in skeletal muscle was increased significantly, while the phosphorylation levels of PI3K, AKT and GLUT4 proteins were slightly decreased. The GAS6 plasma concentrations in the T2DM mouse models were significantly lower than that in the respective control groups, which was irrelevant to genotypes. Surprisingly, the success rate of induction of T2DM in Axl-/- mice was twice as high as that of the wild type mice （P〈0.01）. Conclusion Activation of GAS6/AXL signaling pathway contributes to lower blood glucose and inhibit fatty deposits to a certain extent.

关 键 词：GAS6 AXL信号通路 能量代谢 骨骼肌 葡萄糖转运蛋白4 

分 类 号：Q95-33[生物学—动物学]