Objective

To investigate the regulatory mechanism of Apelin-13-mediated PI3K/AKT signaling pathway in the glucose and lipid metabolism of gestational diabetes mellitus (GDM) mouse.

Methods

GDM mice models were established and treated with Apelin-13 and/or PI3K/AKT inhibitor LY294002. Then, the indicators of glucose and lipid metabolism and the levels of inflammatory factors were detected. Besides, the levels of indicators of oxidative stress in the placenta of mice were measured. Western blotting was also carried out to determine the expression of PI3K/AKT pathway-related proteins in all groups.

Results

In comparison with the Control group, mice in the GDM group presented with the continuous increase in the level of FBG as the time went on, while FINS level decreased evidently. Besides, the fetus alive ratio in the GDM group was much lower with significant increased weight of fetal mouse and weight of placenta; the mice had significant decreased levels of IL-6, IL-1β, TNF-α and MCP-1, and in the placenta, the levels of SOD, GPx, GSH and CAT were also reduced evidently, with significant downregulation of p-PI3K/PI3K and p-AKT/AKT. However, indicators above in the GDM mice treated with Apelin-13 had significant improvement as compared to those in the GDM group, and the improvement was reversed by LY294002 treatment.

Conclusion

Apelin-13, possibly by activating the PI3K/AKT pathway, could improve the glucose and lipid metabolism, reduce the damage caused by oxidative stress and inflammatory reaction, and protect the pancreas islet, thereby improving the pregnancy outcome of GDM mice.

中文翻译：

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Apelin-13介导的PI3K/AKT信号通路在妊娠期糖尿病小鼠糖脂代谢中的调控作用

客观的

探讨Apelin-13介导的PI3K/AKT信号通路在妊娠期糖尿病（GDM）小鼠糖脂代谢中的调控机制。

方法

建立 GDM 小鼠模型并用 Apelin-13 和/或 PI3K/AKT 抑制剂 LY294002 治疗。然后检测糖脂代谢指标和炎症因子水平。此外，还测量了小鼠胎盘中氧化应激指标的水平。还进行了蛋白质印迹以确定所有组中PI3K/AKT通路相关蛋白的表达。

结果

与对照组相比，GDM组小鼠FBG水平随时间持续升高，而FINS水平明显下降。此外，GDM组的胎儿存活率显着降低，胎鼠体重和胎盘重量显着增加；小鼠IL-6、IL-1β、TNF-α和MCP-1水平显着降低，胎盘中SOD、GPx、GSH和CAT水平也明显降低，p-PI3K显着下调/PI3K 和 p-AKT/AKT。然而，与 GDM 组相比，Apelin-13 治疗的 GDM 小鼠的上述指标有显着改善，而 LY294002 治疗逆转了改善。

结论

Apelin-13可能通过激活PI3K/AKT通路，改善糖脂代谢，减少氧化应激和炎症反应造成的损伤，保护胰岛，从而改善GDM小鼠的妊娠结局。