The Studies On The Pathogenesis Of TRB3Involved In Pregnant Rat By High Sucrose And Fat Diet With Abnormal Glucose Tolerance

Background and ObjectivesIncidence of Gestational diabetes mellitus (GDM) is world-widely increasingrecent years, significantly leading to increased economic costs of overall healthcare.Women with GDM are at high risk for pregnancy with complications, such asgestational hypertensive disorders, fetal macrosomia, shoulder dystocia,and cesareandelivery. In addition, GDM constitutes a high risk for type2diabetes mellitus (DM)and cardiovascular disease. The dysfunction of insulin signaling pathway induced bya variety of factors and the apoptosis of pancreatic beta cells mediated byendoplasmic reticulum stress have play an important role in patients withGDM.Except this,oxidative stress,obesity and advancing maternal age contribute toGDM.The recent studys show that Tribbles Homologous protein3(TRB3) widelyaffects the pathogenesis of GDM by signal pathway of TRB3/AKT and CHOP/TRB3.However, less association studies of the pathogenesis with TRB3and GDM duringpregnancy were shown, and it’s to be futher confirmed by this research wether dietaryinterventions effectively reduce insulin resistance and the level of β cell apoptosis.The experiment is to observe the expression of TRB3/AKT in liver tissue andCHOP/TRB3protein in pancreas tissue,and the changes after the dietaryinterventions,is to study the pathogenesis of TRB3participated in abnormal glucose tolerance pregnant rats with high sucrose and fat diet.Subjects and MethodsThirty male SD rats, weighting200g,with control diet during experiment.Onehundred and five healthy female SD rats,weighting200g,forty were fed with controldiet and senventy-five were fed with fat and sucrose diet. After fed with abundantfood and water for six weeks,female rats with both diet were mated overnight, Thefirst day of gestation was defined by spermatozoids under microscopicexamination.Then five groups were randomly divided according to gestation:controldiet virgin rat (NV15rats) group, control diet gestational rat (CG25rats) group, fatand sucrose diet virgin rat (FV15rats) group, fat and sucrose diet gestational rat(FG25rats) group, diet intervention(DI25rats) gourp(fat and sucrose diet beforepregnance,control diet after pregnance). Oral glucose tolerance test（OGTT）wasperformed at the20th day of pregnance. At the21st day of pregnance, food forbiddenonly water allowed for rats,at the22nd day, measured FBG and FINS for HOMA-IR.measured TG、TC and FFA, RT-PCR was performed to detect the expression of TRB3mRNA and AKT mRNA in liver tissue.Westernblot was performed to detect theexpression of TRB3and CHOP protein. On day22of pregnancy, a cesarean sectionwas performed in the three gestational groups. Fetal blood was sampled through anaxillary incision, and pooled; fetuses and placentas were weighed. Fetal plasma wasaliquoted and stored at-20℃for the subsequent measurement of glucose, insulin.SPSS19.0statistical software was used to compare and analyze all datas.Results1.Gestation and high sucrose and fat diet could cause the increase of HOMA-IR,(Fgestation=2318.491,Fdiet=2888.237,Finteraction=993.094,all P＜0.001)2.Gestation and high sucrose and fat diet could cause the increase of TRB3mRNA(Fgestation=256.887,Fdiet=1749.406, Finteraction=2.579all P＜0.001),and thedecrease of AKT mRNA(Fgestation=221.091,Fdiet=1416.984, Finteraction=28.918all P＜0.001);The levels of TRB3mRNA and AKT mRNA among FG group,CG group,andDI group had significant differences（F=445.986and390.334，all P＜0.001）.3. Gestation and high sucrose and fat diet could cause the increase of TRB3protein(Fgestation=475.219,Fdiet=2580.320, Finteraction=206.142all P＜0.001),and also increase of CHOP protein (Fgestation=1275.615,Fdiet=4308.857, Finteraction=245.461all P＜0.001);The levels of TRB3protein and CHOP protein among FG group,CGgroup,and DI group had significant differences（F=764.890and1462.573，all P＜0.001）.4.The weight gain,OGTT data,FBG,Insulin,TG,FFAand TC in FG group weresignificant higher than the other4group.5. Fetal weight was comparable among FG,CG and DI rats, but litter weight washigher in FG rats (P＜0.05) owing to an increase in litter size. Fetal glucose andinsulin levels were not different among the three groups.Placental weight was similarin the three groups.Conclusions1.Rats fed with long-term high-sucrose and fat diet may be exsited in insulinresistance and pancreatic β cell damage or apoptosis,could gradually appear abnormalglucose tolerance, or even in the development of gestational diabetes;2. TRB3may be extensively involved in the pathogenesis of rats with abnormalglucose tolerance fed by high fat and sucrose diet via TRB3/AKT, CHOP/TRB3signaling pathways, and the mechanism may have some interaction;3. Dietary intervention could effectively improve the gestational diabetescondition by changing the signaling pathways which could mediate abnormal glucosetolerance.