Insulin Treatment Cannot Promote Lipogenesis In Fetal Lung In Gestational Diabetes Mellitus

PART?: DETECTION OF LAMELLAR BODY IN AMNIOTIC FLUID USING TWO SETTINGSObjective To compare data of lamellar body count under two analytic settings,and the maturation of fetal lung in gestational diabetes mellitus.Methods98 cases of pregnancy were included,including 30 healthy women(group Ctrl)and 68 cases with gestational diabetes mellitus(group GDM).The lamellar body count(LBC)in amniotic fluid was determined using an automatic cell analyzer under two settings(1-10,and 1-30 ?m).The incidence of neonatal respiratory distress syndrome(RDS)was followed.Results The LBC level in group GDM was less than that in group Ctrl under1-10 ?m setting(P<0.05),the LBC value in group GDM did not differ from that in group Ctrl under 1-30 ?m setting,and a higher incidence of neonatal RDS was noted in group GDM.Conclusions The LBC level under 1-10 ?m setting can be a marker for the maturity of fetal lung,and GDM was a risk factor of neonatal RDS.PART ?: INSULIN TREATMENT CANNOT FAVOR THE MATURITY OF FETAL LUNG IN GESTATIONAL DIABETES MELLITUS RATSObjective To determine whether insulin treatment favor the maturation of fetal lung in GDM rats.Methods Pregnant Sprague-Dawley rats received STZ on day G2.5 to induce GDM,and then rats were randomly divided 3 groups: Ctrl,GDM and Ins(GDM received insulin therapy).Plasma glucose and rat/insulin in maternal and neonatal rats were determined on day G20.5.Neonatal lungs received histological examinations,and lung phospholipids were determined with the molybdenum blue assay.Results Insulin treatment deceased glucose to the normal level before day G9.5,and afterward glucose was with a higher level.Glucose in the maternal plasma in group GDM was higher than that in group Ctrl or Ins.A lower level of rat insulin was detected in maternal and neonatal plasma in group GDM compared with group Ctrl.Human insulin was detected in maternal and neonatal plasma in group Ins.The neonatal lung from group GDM showed a decrease of alveolus with histologic alterations.These alterations partly recovered in group Ins.Ultrastructural inspections demonstrated abnormal AECII and a decrease of lamellar bodies in group GDM or Ins.Phospholipids in the neonatal lung was decreased in group GDM(P<0.05),but insulin treatment failed to increase the level.Conclusions The maturation of fetal lung was delayed in GDM.Insulin treatment cannot favor the maturation of fetal lung in GDM.PART ?: EFFECT OF INSULIN TREATMENT ON THE EXPRESSION OF SREBP-1,SCAP AND INSIG-1 IN FETAL LUNG IN DIABETES MELLITUS IN RATSObjective To determine the effect of insulin treatment on expression of SREBP,SCAP and INSIG-1 genes in the fetal lung in GDM.Methods Lipid droplets in neonatal lung tissues and bronchoalveolar lavage fluid(BALF)cells were observed after oil red O staining,and AECII observed under transmission electron microscope.The expression of SREBP-1,SCAP and INSIG-1 in neonatal lung was determined using immunohistochemical assay,RT-PCR and western blot.Results The intracellular lipid droplets in BALF in groups GDM and Ins were decreased compared with group control(P<0.05),and the level in the group Ins did not differ from that in group GDM.Electron microscopy revealed a decrase of droplets in groups GDM and Ins.Immunohistochemical assay demonstrate a lower expression level of SREBP-1,SCAP,and INSIG-1 in neonatl lung in group GDM(P<0.05),and only SREBP-1 was increased in group Ins(P<0.05).The expression level of SREBP-1,SCAP and INSIG-1was decreased in group GDM(P<0.05),and insulin treatment recovered only the expression of SREBP-1(P<0.05).Conclusions Insulin treatment failed to stimulate lipid synthesis in fetal lung.Insulin treatment only increased the SREBP-1expression.PART ?: INSULIN TREATMENT FAILED TO REDRESS THE IMBALANCE AMONG SREBP-1,SCAP AND INSIG-1Objective To determine whether insulin treatment redress the imbalance among SREBP-1,SCAP and INSIG-1,using isolated alveolar type II epithelial cell (AECII)as a cell modelMethods AECII was isolated from the neonatal lung.Intracellular lipid droplets and the intracellular location of SREBP-1 were observed.The expression of SREBP-1,SCAP and INSIG-1 was detertmined with immunohistochemical assay,RT-PCR and western blot.Results AECII was isolated and identified.Lipid droplets were decreased in AECII from group GDM or Ins.SREBP located in both cytoplasm and nucleus in group Ctrl,but the percentage of doubly stained cells was decreased in AECII from group GDM or Ins(P<0.05).The m RNA/protein level of SREBP-1,SCAP and INSIG-1 was decreased in AECII from group GDM(P<0.05),and insulin treatment increased only the expression level of SREBP-1(P<0.05).Conclusions The nuclear translocation of SREBP-1 protein was impaired in GDM,which cannot be recovered with insulin treatment due to a failure to redress the imbalance among SREBP-1,SCAP,and INSIG-1.