The Relationship Between Insulin Resistance And Expressions Of IRS-1, GLUT4 In Omental Alipose Tissue And Rectus Abdominis In Patients With Gestational Diabetes Mellitus

BackgroundGestational diabetes mellitus (GDM), which is defined as abnormal glucose tolerance of diverse degrees that is first generated or detected during pregnancy, include diabetes mellitus and impaired glucose tolerance, except for those diagnosed as diabetes mellitus before pregnancy. GDM is associated with severe hazards to both pregnant women and fetus. Glucose and lipid metabolism disorders, insulin resistance and obesity are the risk factors of GDM. It is well know that the pathogenesis of gestational diabetes mellitus is mainly due to insulin resistance. Abnormal insulin signaling pathway can induce insulin resistance directly. Insulin resistance contains the levels of pre-receptor, receptor and post-receptor. It is well know that the important reason of insulin resistance is the handicap after insulin receptor in insulin signaling pathway. Insulin receptor substrate 1 and glucose transporter 4 are two important molecules after insulin receptor in insulin signaling pathway, and have significant meaning in insulin resistance.ObjectiveIn the study, we investigated the expression of IRS-1 and GLUT4 in omental adipose and rectus abdominis muscle tissue in patient with GDM in order to observe if the level of expression correlated with insulin resistance in the pathogenesis of GDM.Material and MethodsUsing the WHO standard for GDM dignosis. All subjects were divided into three groups:Gestational diabetes mellitus group(GDM), normal gravida group(NG) and normal non-gravidity group(NNG). The study have measured followed parameters such as blood pressure, pre-gestational weight, FPG, FINS, TC, TG and so on. The levels of IRS-1 and GLUT4mRNA in omental adipose tissue and rectus abdominis tissue were measured by reverse transcription-polymerase chain reaction (RT-PCR). We compared and analyzed levels of FPG, FINS, HOMA-IR, IRS-1 and GLUT4mRNA in three groups with SPSS 10.0 statistic software. The relationships between each index were analyzed to testify their internal correlation with insulin resistance.Results(1)The levels of FINS, HOMA-IR, TC and TG increased significantly from normal non-gravidity, normal gravida to gestational diabetes mellitus women(P<0.05). The level of FPG is higher in GDM group comparing with NG group and NNG group(P<0.01), parameters in the other two groups were not significantly difference compared with NG groups (P>0.05).(2)The mRNA expression of IRS-1 and GLUT4 in omental adipose tissue decreased significantly from normal non-gravidity, normal gravida to gestational diabetes mellitus women (0.633±0.058,0.450±0.034,0.280±0.039, P<0.01; 0.702±0.044,0.589±0.043,0.355±0.040, P<0.01).(3) The mRNA expression of IRS-1 in rectus abdominis tissue decreased significantly from normal non-gravidity, normal gravida to gestational diabetes mellitus women(0.324±0.043,0.267±0.045,0.186±0.045, P<0.01). No difference of GLUT4mRNA expression in rectus abdominis tissue was found among normal non-gravidity, normal gravida and gestational diabetes mellitus women(P>0.05).(4)In omental adipose tissue of all subjects, IRS-1mRNA correlated positively with GLUT4mRNA.(5)There was significantly correlation within HOMA-IR and IRS-1, GLUT4mRNA.Conclusions1. Physiologic insulin resistance exist in normal pregnant women. Gestational diabetes mellitus women exist more severe insulin resistance compared with normal pregnant women.2. In Gestational diabetes mellitus women, the mRNA expression of IRS-1 and GLUT4 in omental adipose tissue decreased significantly, the mRNA expression of IRS-1 in rectus abdominis tissue also decreased significantly. It demonstrated that IRS-1 and GLUT4 may have closed relation with the pathogenesis of GDM.3. In Gestational diabetes mellitus women, there were some disabilities in transcription of GLUT4 that decreased the ability of adipose cell to transport and utilize glucose in omental adipose tissue. The insulin resistance in rectus abdominis tissue may associate with the translation of GLUT4.4. The decrease of the mRNA expression of IRS-1 was accompanied by the decrease of GLUT4. IRS-1mRNA was correlated positively with GLUT4mRNA.5. The mRNA expressions of IRS-1 and GLUT4 were important factors which influence HOMA-IR.