妊娠期糖尿病(GDM)是一种在怀孕期间发生的代谢性疾病。在这里,我们研究了G蛋白偶联受体1(GPR1)通过丝氨酸/苏氨酸激酶(AKT)途径磷酸化介导GDM的作用。将30只妊娠SD大鼠分为:正常妊娠对照组(NC),GDM模型组,GDM模型+高剂量GPR1拮抗剂治疗(GDM+Ari)组。建立GDM模型,GDM+Ari组采用GPR1拮抗剂阿立哌唑。血糖水平,胰岛素水平,检测胰岛素抵抗(IR)。GPR1、AKT的表达和磷酸化,使用逆转录聚合酶链反应(RT-PCR)和蛋白质印迹(WB)检测胎盘组织中的细胞外信号调节激酶(ERK)。血清胰岛素浓度,葡萄糖浓度,GDM组SD大鼠妊娠期糖化血红蛋白浓度明显高于NC组(P<0.05)。GPR1、AKT的表达和磷酸化水平,GDM组SD孕鼠胎盘组织中ERK含量明显低于NC组。此外,与GDM组相比,GPR1、AKT、GDM+Ari组胎盘组织ERK显著降低,同时提高血糖水平和IR水平。此外,生存数量,体重,GDM+Ari组子代畸形率明显提高,对后代数量没有显著影响。GPR1、AKT、胎盘组织中的ERK表现出显著下降,而GDM+Ari组的葡萄糖水平和IR升高。增强GPR1的表达可能会激活AKT磷酸化以减轻GDM。GPR1有可能成为糖尿病治疗的新靶点。提供管理GDM的新见解。
Gestational diabetes mellitus (GDM) is a metabolic disease that occurs during pregnancy. Herein, we investigate G protein-coupled receptor 1 (GPR1) in mediating GDM through the phosphorylation of serine/threonine kinase (
AKT) pathway. Thirty pregnant SD rats were grouped into: normal pregnancy control group (NC), GDM model group, and GDM model + high-dose GPR1 antagonist treatment (GDM + Ari) group. GDM model was established, and the GDM + Ari group adopted GPR1 antagonist aripiprazole. The blood glucose level, insulin level, and insulin resistance (IR) were detected. The expression and phosphorylation of GPR1, AKT, and extracellular signal-regulated kinase (ERK) in placental tissue were detected using reverse transcription-polymerase chain reaction (RT-PCR) and western blotting (WB). The serum insulin concentration, glucose concentration, and glycated hemoglobin concentration during pregnancy in GDM group SD rats were significantly higher than those in the NC group (P < 0.05). The expression and phosphorylation levels of GPR1,
AKT, and ERK in the placental tissue of SD pregnant rats in the GDM group were significantly lower than those in the NC group. Furthermore, compared with the GDM group, the expression of GPR1,
AKT, and ERK in placental tissue was significantly reduced in the GDM + Ari group, while simultaneously enhancing the blood glucose level and IR level. In addition, the survival number, body weight, and malformation rate of the offspring of the GDM + Ari group were significantly improved, and there was no significant effect on the number of offspring. The expressions of GPR1,
AKT, and ERK in placental tissue exhibited a significant decrease, while the glucose level and IR were observed to increase in the GDM + Ari group. Enhancing the expression of GPR1 may activate
AKT phosphorylation to alleviate GDM. GPR1 could potentially serve as a novel target for diabetes treatment, offering new insights into managing GDM.