| Background and ObjectivesGestational diabetes mellitus(GDM)is defined as a special type of diabetes mellitus.There are many similarities in the etiology and pathology of type 2 diabetes mellitus.It has long been recognized that insulin resistance during pregnancy should be the major pathological mechanisms,which led to GDM.Insulin integrated with insulin receptor,after the functioning of signaling molecule in cells,which results in signaling transmission within cells,effectors created physiological effect. Insulin signal t ransduction is crucial to insulin physiological function.The dysfunction of insulin-signaling transmission weakens insulin physiological function,and leads to insulin resistance.This study was designed to observe the expression of PI3K and P-AKT protein and their association with pathological features in the placenia issue of the normal full-term pregnancy and GDM,which were seen as the key molecules in the insulin receptor signal transduction.To analyse the relationship of insulin resistance and GDM,in order to clarify the role of PI3K and P-AKT protein in the pathogenesis of GDM and explore the defects in insulin post receptor signal transduction which may be the pathological basis of GDM.MethodsThe expression of PI3K and P-AKT protein was investigated in the placenia issue using immunohistochemical staining in 60 case,including 30cases of normal full-term pregnancy as control and 30cases of GDM.We detected the levels of serum glucose,serum insulin, total cholesterol,triglyceride and HbAlc.IR index including HOMA-IR,HOMA-β%,HOMA-ISI was calculated with homeostasis model assessment(HOMA),and insulin resistance was evaluated.These parameters were classified and matched statistically.The expression of PI3K and AKT in GDM and the clinicopathological characteristics were studied with Spearman grade relevance analyse.Results1.The positive rates of PI3K in the placenia issue of GDM and normal pregnant women were 70%(21/30)and 100% respectively. The expression of PI3K in diabetic placenta was distinctly lower than that in control group,the difference of which between the experimental group and control group was significant.2.The positive rates of P-AKT in the placenia issue of GDM and normal pregnant women were 56.67%(17/30)and 96.67% respectively.The expression of P-AKT in diabetic placenta was distinctly lower than that in control group,the difference of which between GDM group and control group was significant.3.The expression of PI3K was positively correlated with that of P-AKT in gestational diabetic placental(r=0.37, P= 0.04).4.Compared with maternal serum in normal pregnaney,higher concent-rations of maternal serum FBG,FINS, HbAlc and HOMA-IR as well as lower HOMA-ISIand HOMA-β% in GDM were observed(P<0.001).5.In GDM group a higher trend of maternal serum concentrations of TG and TC were found,companied with a higher trend of pre-pregnancy body mass index(BMI)(24.54±3.19 kg/m2 vs 21.46±2.62 kg/m2).6. There was a negative correlation between PI3K and HOMA-IR as well as BMI in GDMgroup(r=-0.413,-0.420, P=0.023,0.021). On the other hand,there was also a negative correlation between P-AKT and TG in GDM group(r=-0.380, P=0.039).ConclusionsThere is the material basis of insulin/PI3K/AKT signaling pathway in the placenia issue during pregnany.Compared with the normal full-term pregnancy, The down-reg ulated expression of PI3K and P-AKT protein in the placentas of gestational diabetes m llitus may be one of the molecule mechanisms postreceptor signal transduction obstacle and IR in GDM.At the same time the decline of the expression amount of PI3K in GDM patients was negatively correlated with HOMA-IR,which further suggests the abnormal expression of PI3K by affecting insulin resistance play a key role in the occurrence and progress of GDM.PI3K was the major upstream signaling molecules of AKT,whose change showed a positive correlation with AKT. PI3K may be the main reason causing the barriers of transmission.The cascade effect of PI3K and P-AKT protein was important in the development process of GDM.The risk for developing GDM was increasing with growth rate of pre-pregnancy body mass index and hypertriglyceridemia,which perhaps affected the expression of key proteins of insulin receptor signaling pathway...
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