GDM And Excessive Weight Gain Alter Insulin Signaling In Skeletal Muscle And Subcutaneous Adipose Tissue

Objective:To investigate the expression of key components of insulin signaling and glucose transporters in the skeletal muscle and adipose tissue from pregnant women with gestational diabetes mellitus (GDM) and the impact of excessive weight gain on insulin signaling in adipose tissue of pregnant women .Methods: Small amount of rectus abdominis was obtained via a biopsy during cesarean section from 15 pregnant women with normal glucose tolerance and increase of body mass index (BMI) as 4kg/m2 approxmately (NGT1) and pregnant women with normal glucose tolerance and increase of BMI as 8kg/m2 approximately (NGT2) and GDM. Muscle and adipose tissue were divided into two sections and incubated in the culture medium with or without insulin for 30 minutes. mRNA levels of insulin receptor substrate 1 (IRS-1), IRS-2, glucose transporter 2 (GLUT-2), and GLUT-4 were detected by quantitative real time PCR and protein levels of protein kinase B (Akt), phosphorylation of Akt (P-Akt), and GLUT-4 were examined by Western blot. Fasting blood glucose and fasting insulin levels was detected by Glucose oxidase and enzyme-linked immunosorbent assay (ELISA),then calculate insulin resistance index and insulin secretion index according to the literature.Results: 1. In skeletal muscle, in basal state, the IRS-1, IRS-2 and GLUT-2 mRNA levels in GDM group were significantly lower than those in NGT1 group (P<0.05); GLUT-4 mRNA expression did not differ in basal state, but insulin stimulated upregulation of GLUT-4 was significantly attenuated in GDM group.2. Compared with the NGT1 group, protein levels of GLUT-4 in GDM group were significantly decreased in both basal state and stimulation with insulin; Insulin induced P-Akt was significantly decreased in GDM group.3.In adipose tissue, in basal state, the protein expression of GLUT-4 in GDM group and NGT2 group was significantly lower than NGT1 group (P <0.05); after insulin stimulation, the level of GLUT-4 protein expression in NGT1 group was increased more than NGT2 group or the GDM group (P <0.05). 4. In basal state, the protein expression of Akt were not significantly different among the three groups (P >0.05); after insulin stimulation, compared with the baseline state, Akt phosphorylation significantly was increased in NGT1 group (P <0.05), while the NGT2 group and the GDM Group did not change much (P >0.05).Conclusion: 1.GDM patients had transcriptional and translational defects in key components of insulin signaling pathway in skeletal muscle, which contributes to the pathogenesis of insulin resistance.2. The excessive weight gain in normal glucose tolerance pregant women almost share a similar expression with GDM women in the insulin signaling and glucose transpoter performance, which will further explore the etiology of GDM and maternal type 2 diabetes in the future, it also have far-reaching significance to enhance nutritional guidance in order to prevent excessive weight gain during pregnancy.