Effect of GAS6/AXL signaling pathway inactivation on energy metabolism in mice
Received:September 26, 2013  
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KeyWord:GAS6/AXL signaling pathway;Energy metabolism;Skeletal muscle;Glucose transporter 4;Mouse
高娟 首都医科大学基础医学院, 北京
郭萌 首都医科大学基础医学院, 北京
霍学云 首都医科大学基础医学院, 北京
李振坤 首都医科大学基础医学院, 北京
张双悦 首都医科大学基础医学院, 北京
杜小燕 首都医科大学基础医学院, 北京
王超 首都医科大学基础医学院, 北京
陈振文 首都医科大学基础医学院, 北京
王钜 首都医科大学基础医学院, 北京
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      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.
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