The Primary Study Of Adiponectin And Its Receptors In The Development Of Insulin Resistance

Objective:To primarily study the function of adiponectin and its receptors in procession of IR, and the effect of pioglitazone on their mRNA expression, sequently in 3 level: humanity, rat model and cultured cell. This thesis conclude 4 parts: 1 , The change and effecting factors of plasma adiponectin level in old subjects with abnormal glucose tolerance; 2, The distribution of adiponectin receptors in Wistar rat; 3, The effect of fat-fed and pioglitazone on mRNA expression of adiponectin with its receptors; 4, The effect of FFA and pioglitazone on the expression of adiponectin with its receptors in HepG2 cell.Subjective and methods:1. Examine weight, waistline, hipline, blood pressure, lipid profile, MDA, PAI-1, CRP and adiponectin in total 87 people aged above 60, which including normal glucose tolerance(NGT), impaired glucose tolerance(IGT) and diabetic(DM) according WHO criterions. Divide all the subjects into 2 groups at the median of adiponectin concentration: lower and higher adiponectin group, compare the above indexes.2. Kill normal Wistar rat and divide equal weight of cardiac muscle, skeletal muscle, liver, kidney, testicle and fat. Extract total RNA and RT-PCR, half-quantitative analysis the expression of R1/2 in different organize.3. 45 Wistar male rats were randomly distributed into 3 groups:control, fat-fed(HF) and pioglitazone group. 11 weeks later, extract total RNA, RT-PCR and half-quantitative analysis using PCR and Southern Blotting.4. HepG2 cell was randomly divided into 8 equivalent groups, including control group, pioglitazone group, 3 groups treated with different concentration of palmitic acid(PA), and 3 groups accordingly treated with above concentration PA plus pioglitazone . Then incubating 24 hours, extracted total RNA, RT-PCR and half-quantitative analysis the expression of R1/2.Results:1.Adiponectin ran down gradually from IGT to DM. Our data showed that in lower adiponectin group NGT was obviously fewer, while DM was much more than higher group, as well as plasma glucose. Logistic Analysis revealed that HDL and FBS were independent risk factors that influenced plasma adiponectin level.2. R1 mRNA was observed in rat cardiac muscle, skeletal muscle, liver, kidney, testicle and fat, with the most expression in testicle and fat (P<0.01). While R2 mRNA was only detected in liver, kidney and skeletal muscle, which expressed most in liver (P<0.01).3. In HF group , weight, FBS , FFA, insulin and HOMA-IR increased obviously than control group, while the glucose , insulin tolerance and adiponectin , resistin reduced greatly (P<0.01). In pioglitazone group, insulin and HOMA-IR were significantly lower than HF group (P<0.01) ; while the expression of adiponectin and resistin of pioglitazone group increased markedly (P<0.05) .The expression of adiponectin receptor 1 (Rl) also showed the same tendency among three groups, but didn't achieve significant statistic differences.