妊娠期糖尿病患者肌肉组织中胰岛素信号转导和GLUT-4表达的变化

目的研究妊娠期糖尿病(gestational diabetes mellitus,GDM)孕妇肌肉组织中胰岛素信号通路及葡萄糖转运蛋白表达的变化,探讨其在GDM发病过程中的作用。方法将40例孕妇分为糖耐量正常(NGT)组和GDM组,每组20例,分离少量腹直肌,分别置于含和不含胰岛素的培养液中温育30 min。用Real-time PCR法检测胰岛素受体底物1(insu-lin receptor substrate 1,IRS-1)、胰岛素受体底物2(IRS-2)、葡萄糖转运蛋白2(glucose transporter 2,GLUT-2)、葡萄糖转运蛋白4(GLUT-4)mRNA的表达,Western blot检测蛋白激酶B(Akt)的磷酸化程度、GLUT-4蛋白水平的变化。结果①基础状态时,GDM组IRS-1、IRS-2和GLUT-2 mRNA表达较NGT组降低(P<0.05);GLUT-4 mRNA表达2组无统计学差异(P>0.05);经胰岛素刺激后,NGT组中GLUT-4 mRNA较基础状态升高(P<0.05),而GDM组则无明显变化(P>0.05)。②NGT组经胰岛素刺激后,Akt蛋白的磷酸化程度明显增高(P<0.05),GDM组无明显变化(P>0.05);基础状态时,GDM组与NGT组相比,GLUT-4蛋白表达明显降低(P<0.05);经胰岛素刺激后,GLUT-4蛋白的表达水平均增高,NGT组增加的幅度明显高于GDM组(P<0.05)。结论 GDM患者胰岛素信号通路中的关键效应分子存在转录或翻译水平的缺陷,对胰岛素的反应降低,导致胰岛素抵抗。

Transduction of insulin signals and expression of glucose transporter 4 in skeletal muscle of women with gestational diabetes mellitus

Objective To study the transduction of insulin signals and the expression of glucose transporter in skeletal muscle of women with gestational diabetes mellitus(GDM) and the role of GDM in development of diseases.Methods Forty pregnant women were divided into normal glucose tolerance(NGT) group and GDM group,20 women in each group.A small amount of rectus abdominis was isolated and placed into a culture medium with or without insulin.mRNA expression levels of insulin receptor substrate 1(IRS-1),IRS-2,glucose transporter 2(GLUT-2),and GLUT-4 were measured by real time PCR.Phosphorylation of protein kinase B(Akt) and expression level of GLUT-4 were assayed by Western blotting.Results The expression levels of IRS-1,IRS-2 and GLUT-2 mRNA in basal state were significantly lower in GDM group than in NGT group(P<0.05) and no significant difference was observed in expression of GLUT-4 mRNA between the two groups.However,after insulin stimulation,the expression level of GLUT-4 mRNA in basal state was significantly higher in NGT group than in GDM group(P<0.05),while the phosphorylation of Akt and the expression level of GLUT-4 were significantly lower in GDM group than in NGT group(P<0.05).Conclusion Defects of key effector molecules at transduction and translation levels in the insulin signaling pathway of GDM patients can reduce the reaction to insulin,thus leading to insulin resistance.