Department of Obstetrics and Gynecology, Jingzhou Central Hospital, Jingzhou City 434020, Hubei Province, PR China.
Department of Obstetrics and Gynecology, Jingzhou Central Hospital, Jingzhou City 434020, Hubei Province, PR China.
Immunobiology. 2021 Sep;226(5):152135. doi: 10.1016/j.imbio.2021.152135. Epub 2021 Sep 1.
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.
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.
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.
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.
探讨 Apelin-13 介导的 PI3K/AKT 信号通路对妊娠期糖尿病(GDM)小鼠糖脂代谢的调控机制。
建立 GDM 小鼠模型,并给予 Apelin-13 和/或 PI3K/AKT 抑制剂 LY294002 处理,检测各组小鼠的糖脂代谢指标及炎症因子水平,检测各组小鼠胎盘组织中氧化应激指标水平,Western blot 法检测各组小鼠胎盘组织中 PI3K/AKT 通路相关蛋白的表达。
与对照组比较,GDM 组小鼠随着时间的推移,FBG 水平持续升高,而 FINS 水平明显降低;GDM 组活胎比例明显降低,胎鼠体重及胎盘重量明显增加,血清中 IL-6、IL-1β、TNF-α 和 MCP-1 水平明显降低,胎盘组织中 SOD、GPx、GSH 和 CAT 水平明显降低,p-PI3K/PI3K、p-AKT/AKT 表达明显下调;而给予 Apelin-13 处理后,上述指标均明显改善,给予 LY294002 处理后,改善作用被逆转。
Apelin-13 可能通过激活 PI3K/AKT 通路,改善 GDM 小鼠的糖脂代谢,减轻氧化应激和炎症反应所致的损伤,保护胰岛,从而改善 GDM 小鼠的妊娠结局。