The Study Of Adiponectin With Its Receptors And The Role Of Rosiglitazone On Adiponectin Receptors In Liver

Objective①To establish impaired glucose tolerance(IGT) animal model.②To study the function of adiponectin(APN) and adiponectin receprors (AR) in procession of insulin resistance(IR),and the effect of Rosiglitazone(ROS) on AR'S mRNA expression,Humanity,rat model and cultured cells were studied sequently.The study included four parts:(1) The change and affect factors of plasma adiponectin level in people with impaired glucose regulating(IGR).(2) The change and affect factors of plasma adiponectin,adiponetin receptoos mRNA in liver of Wistar rat's with IGT.(3) The effect of fat-fed and Rosiglitazone on mRNA expression of adiponetin with its receptors.(4) The effects of free fat aid(FFA) and Rosiglitazone on the expression of adiponectin receptors in HepG2 cells.MethodsTotal 122 people were recruited,which included 60 people with normal glucose tolerance(NGT) and 62 people with impaired glucose tolerance(IGT).Oral glucose Tolerance test(OGTT) were tested in all people.1.The body weight,waistline,hipline,blood pressure and B ultrasound in Liver were measured.The body mass index(BMI) and waistline/hipline ratio(WHR) were calculated.Plasma insulin, adiponectin,PAI-1 and c raction protein(CRP) were examined by using ELISA.Assessed the degree of insulin resistance by using homeostasis model assessment of insulin resistance(HOMA-IR). The hepatic pathological changes were observed by suing light microscope.2.Fourty Wistar male rats were randomly divided into 2 groups: control group and fat-fed(HF) group.Adiponectin receptor were examined by reverse transcription-polymerse chain raction(RT-PCR). AR protein were measure by western blotting.3.Sixty male Wistar rats were randomly distributed into 2 groups: including control group 10 rats and HF group 50 rats.In HF group, 20 rats were fed with Rosiglitazone(3mg/kg·d) and other 20 rats were fed with Metformin(300mg/kg·d) AR1 and AR2 mRNA of liver were examined by RT-PCR.4.HepG2 cells were randomly divided into 8 equivalent groups, including control group,Resiglitazone group,3 groups treated with different concentration of palmitic acid(PA) and 3 groups accordingly treated with above concentration PA plus Rosiglitazone. Then incubating 24 hours,extracted total RNA,RT-PCR and half quantitative analysis the expression of AR1 and AR2 mRNA.Results1.People with IGT had lower adiponectin compared with people with NGT.HDL and FPG were independent risk factors that influenced plasma adiponectin level.2.In HF group,weight,visceral fat content / weight ratio(VF/W), FPG,Insulin and HOMA-IR were higher than that in control group. Adiponectin was lower than the control group.AR1 and AR2 mRNA and protein in liver were decreased in HF group.When treated with Rosiglitazone for 8 weeks and 12 weeks,AR1 and AR2 mRNA of liver increased obviously.3.mRNA expression of AR2 decreased in groups treated only with PA,especially in the groups over 200 umol/L.While in PA+ROS groups,all AR2 mRNA were higher than corresponding PA groups, particularly in groups which PA above 200 umol/L.Conclusions1.The decline of plasma adiponectin may play an importaut role in the development of impaired glucose tolerance in people and Wistar rats.2.The expressions level of adiponectin and its receptors are closely associated with the development of obesity,high plasma free acid and IR.Rosiglitazone can increase the expression of AR mRNA, especially AR2 mRNA.3.The increased expression of AR2 mRNA play a key role in Rosiglitazone induced insulin sensitivity amelioration.