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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 effect of inactivation of growth arrest-specific gene 6 (GAS6) signaling pathway on maintaining energy homeostasis in mice. Methods Axl knockout (Axl - / -) mice and its wild type (Axl + / +) mice, the main GAS6 receptor, were used as research objects. The blood glucose, blood lipid, Muscle glyco-metabolism signal protein PI3K, AKT and glucose transporter 4 (GLUT4) gene expression levels and protein phosphorylation levels of the difference between; Simultaneous detection of artificially induced type 2 diabetes (type 2 diabetes mellitus, T2DM) modeling There was a correlation between serum GAS6 protein levels in pre-and post-mice and changes in the modulo of T2DM model. Results The blood lipid of Axl - / - mice fluctuated abnormally, and the fat deposition rate was significantly higher than that of wild type mice (P <0.01). The ability of Axl - / - mice impaired the regulation of blood glucose, the fasting blood glucose level of Axl - / - mice was significantly higher than that of wild type and Glut4 mRNA of skeletal muscle, while the phosphorylation of PI3K, AKT and GLUT4 decreased slightly. After induced by T2DM, the GAS6 concentration in the plasma of Axl + / + and Axl - / - mice was significantly lower than that of the control group, and the rate of molding in Axl - / - mice T2DM model was twice that of Axl + / + mice (P <0.01). Conclusion Activation of GAS6 / AXL signaling pathway may reduce blood glucose and inhibit fat deposition to a certain extent.