The Investigation Of Correlation Between The Expression Of Mammalian Target Of Rapamycin In Serum,Placenta And Abdominal Subcutaneous Fat Tissue And Gestational Diabetic Mellitus

Objective To assess the expression of mammalian target of rapamycin(m TOR)in gestational diabetes mellitus(GDM)and normal pregnant women’s serum.And to investigate the expression of mammalian target of rapamycin and 2 phosphorylated downstream targets of m TOR,ribosomal protein S6 kinase(p70S6K)and eukaryotic initiation factor 4E-binding protein 1(p-4EBP1)in placenta and fat tissue in gestational diabetic patients for evaluating the relationship of m TOR and pathogenesis in gestational diabetes mellitus.Methods(1)The serum of pregnant women were taken from Shengjing hospital between Jun.2016 and Oct.2017.According to the results of OGTT test at 24-28 weeks of pregnancy,the cohort were divided into the GDM group and the control group.m TOR protein expression of the serum samples was measured by ELISA.(2)The cohort of pregnant women for cesarean section,taken from Shengjing Hospital of China Medical University from June 2017 to June 2018,were divided into the gestational diabetic mellitus(GDM)group and the control group(n=8 each).m TOR,p70S6 K and p-4EBP1 m RNA and protein expression in placenta and abdominal subcutaneous fat tissue were analyzed and quantified by q RT-PCR and Western blot.Immunohistochemistry was used to detect the localization of m TOR protein in tissues.(3)The clinical data and the test results of the two groups were analyzed by independent sample t test or Mann-Whitney U test.Results(1)In the serum cohort,the average body mass index of pregnant women in the gestational diabetes group and the normal control group was 26.85 kg/m2 and22.85 kg/m2,respectively,the difference was statistically significant(P=0.003);fasting blood glucose in the GDM group,1 hour postprandial blood glucose,and postprandial 2h blood glucose and glycated albumin were significantly higher than the normal control group(P<0.001),glycated hemoglobin was significantly increased in the GDM group(P=0.001).The median hemoglobin content of the GDM group was 125.5 g/L,which was higher than that of the normal control group(119 g/L),and the difference was statistically significant(P=0.014).The expression level of m TOR protein in serum of the GDM group was significantly higher than that of the control group P< 0.05).(2)In the cesarean section cohort,Body mass index(BMI)and fetal birth weight in GDM group were significantly higher than those in normal control group(30.9±4.9 vs 25.9±4.2,P=0.003;3825±419.3 vs 3251±290.0,P=0.013).The expression of m TOR,p70S6 K and p-4EBP1 m RNA in placenta of the GDM group were significantly higher than those in the control group,respectively(P=0.047,P=0.002,P=0.001).Meanwhile,the m RNA and protein expression of m TOR,p70S6 K and p-4EBP1 increased significantly in abdominal subcutaneous fat tissue of the GDM group(P=0.031,P=0.001,P=0.013).Compared with control group,the protein expression of m TOR,p70S6 K and p-4EBP1 in placenta of the GDM group were also higher(P=0.009,P=0.04,P=0.046).Likewise,both the m RNA and protein expression of m TOR,p70S6 K and p-4EBP1 increased significantly in abdominal subcutaneous fat tissue of the GDM group(P=0.032,P=0.047,P=0.041).Although m TOR protein was localized in the placenta tissue and abdominal subcutaneous fat tissue in both the GDM group and the control group,more was observed in the GDM group.Conclusion The increased expression of m TOR and downstream p70S6 K and p-4EBP1 in serum,placenta and fat tissue suggested that m TOR activity may be involved in changes of gestational diabetes mellitus.