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目的:研究妊娠期糖尿病(gestational diabetes mellitus GDM)患者肌肉组织中磷脂酰肌醇3激酶(PI-3K)的活性变化与葡萄糖转运蛋白4(GLUT4)跨膜易位的相关性,探讨它们在妊娠期糖尿病发病机制中的作用。方法:RT-PCR法检测25例GDM患者(GDM组)、26例糖耐量正常孕妇(对照组)肌肉组织中GLUT4 mRNA的表达,western blot法检测各组肌肉组织细胞外膜上GLUT4易位的变化,采用ELISA法检测两组肌肉组织PI-3K的活性,并分析PI-3K的活性变化与GLUT4易位的相关性,采用葡萄糖氧化酶法检测两组空腹血糖(FPG)水平。结果:①基础状态和胰岛素刺激后GDM组和对照组肌肉组织GLUT4 mRNA的表达分别为(0.71±0.02,0.50±0.04)、(0.76±0.03,0.55±0.01),两组比较差异无统计学意义(P>0.05)。②基础状态和胰岛素刺激后GDM组GLUT4跨膜易位分别为(0.61±0.05,0.40±0.03),明显低于对照组(0.93±0.02,0.71±0.04),差异有显著性(P<0.01)。③基础状态和胰岛素刺激后GDM肌肉组织中PI-3K的活性为(3.1±0.2,2.1±0.3),明显低于正常妊娠组(5.2±0.5,3.0±0.6),二者比较差异有显著性,GLUT4跨膜易位与PI-3K活性呈明显正相关(r=0.76,P<0.01)。结论:GDM患者肌肉组织中GLUT4的易位降低与PI-3K的活性下降具有关联性,PI-3K的活性下降是GLUT4的易位降低导致GDM胰岛素抵抗的原因之一,参与了GDM的发病。
OBJECTIVE: To investigate the relationship between the changes of phosphatidylinositol 3-kinase (PI-3K) activity and glucose transporter 4 (GLUT4) transmembrane translocation in patients with gestational diabetes mellitus (GDM) The role of diabetes in the pathogenesis. Methods: The expression of GLUT4 mRNA in 25 GDM patients (GDM group) and 26 pregnant women with normal glucose tolerance (control group) was detected by RT-PCR. The GLUT4 translocation in the muscle cells of each group was detected by western blot The activity of PI-3K in muscle tissue of the two groups was detected by ELISA. The correlation between the changes of PI-3K activity and GLUT4 translocation was analyzed. The fasting blood glucose (FPG) levels were detected by glucose oxidase. Results: (1) The expression of GLUT4 mRNA in muscle tissue of GDM group and control group were (0.71 ± 0.02,0.50 ± 0.04) and (0.76 ± 0.03,0.55 ± 0.01) respectively after basal state and insulin stimulation, there was no significant difference between the two groups (P> 0.05). (2) The translocation of GLUT4 in GDM group was (0.61 ± 0.05, 0.40 ± 0.03) and significantly lower than that in the control group (0.93 ± 0.02, 0.71 ± 0.04) respectively after basal state and insulin stimulation (P <0.01) . ③ The basal state and insulin stimulated PI-3K activity in GDM muscle was (3.1 ± 0.2, 2.1 ± 0.3), which was significantly lower than that in normal pregnancy group (5.2 ± 0.5, 3.0 ± 0.6), the difference was significant There was a significant positive correlation between GLUT4 transmembrane translocation and PI-3K activity (r = 0.76, P <0.01). CONCLUSIONS: The decrease of GLUT4 translocation in muscle tissue of GDM patients is associated with the decrease of PI-3K activity. The decrease of PI-3K activity is one of the reasons that GLUT4 translocation reduces the insulin resistance of GDM, which is involved in the pathogenesis of GDM.