Regulatory role of Apelin-13-mediated PI3K/AKT signaling pathway in the glucose and lipid metabolism of mouse with gestational diabetes mellitus

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-1 beta, TNF-alpha 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.