The Relationship Between Insulin Resistance And Exprission Of IRS-1and GLUT4in Palcenta Of 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,is a special type of diabetes.GDM is associated with severe hazards to both mothers and fetus, and the majority of patients with GDM will eventually develop to type2diabetes. It is well known that the pathogenesis of gestational diabetes mellitus is mainly due to insulin resistance.Abnormal insulin signaling pathway can lead to insulin resistance directly.Insulin resistance contains the levels of pre-receptor, receptor and post-receptor. The current study found that there is no difference in receptor levels in GDM and the normal. It is well known that the important reason of insulin resistance is the handicap after insulin receptor in insulin signaling pathway. Insulin receptor substrate1and glucose transporter4are 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-1and GLUT4in placenta in patient with GDM in order to observe the level of expression correlated with insulin resistance in the pathogenesis of GDM.MethodsThe expression of IRS-1and GLUT4protein was investigated in the placental tissue using immunohistochemical staining in56case,including26cases of normal full-term pregnancy as control and30cases of GDM. We detected the levels of fasting blood glucose,fasting insulin,total cholesterol and triglyceride. IR index including HOMA-IR、HOMA-β%、HOMA-ISI was calculated with homeostasis model assessment(HOMA),and insulin resistance was evaluated.All relevant information was statistical analyzed.Results1.There was no statistical difference in age, gestational age, and blood pressure between two groups(P>0.05). The body mass index,the weigth of the fetus of GDM group were higher than those of control group(P<0.01).2.Fasting blood glucose,fasting insulin,total cholesterol and triglyceride of GDM group were higher than those of control group(P<0.01) insulin resistance index of GDM group were higher than those of control group(P<0.001).While the insulin sensitivity index,β-cell function of GDM group were lower than those of control group(P<0.01).3.The positive rates of IRS-1in the placental tissue of GDM and normal pregnant women were66.7%(20/30) and100%respectively.The expression of IRS-1in diabetic placenta was distinctly lower than that in control group,the difference of which between the experimental group and control group was significant.4.The positive rates of GLUT4in cytoplasm in the placental tissue of GDM and normal pregnant women were90%(27/30) and85.2%(23/26) respectively, there was no statistical difference(χ2=4.87, P>0.05). The positive rates of GLUT4in membrane in the placental tissue of GDM and normal pregnant women were53.3%(16/30) and84.6%(22/26) respectively,the difference of which between GDM group and control group was significant (χ2=15.62,P<0.01)5.The expression of IRS-1was positively correlated with that of GLUT4in gestational diabetic placenta(r=0.46,P<0.01).6.There was a negative correlation between IRS-1and HOMA-IR (r=-0.562, P=0.001).On the other hand, there was also negative correlation between GLUT4in membrane and HOMA-IR,BMI,TG in GDM group(r=-0.491,P=0.005; r=-0.402,P=0.030; r=-0.475,P=0.006).Conclusion:There is physiological insulin resistance in normal pregnancy,while GDM patients have severe insulin resistance.IRS-1and GLUT4expressed in normal pregnancy placenta syncytiotrophoblast cells, indicating that the two physiological processes involved in normal pregnancy. The decreased expression of IRS-1protein accompanied by decreased GLUT4translocation, indicating that the damaged insulin singal transduction can cause damage to post-receptor pathway, leading to insulin resistance and the occurrence of GDM.The expression of GLUT4in GDM and normal pregnancy have no obvious difference,but both in the membrane translocation was significantly difference, indicating that insulin resistance may be related with the translocation of GLUT4.The decreased expression of IRS-1and translocation of GLUT4are likely to affect HOMA-IR. Body mass index may be risk factors to GDM.