The Relationship And Mechanisms Rbetween Glucolipid Metabolism And Plasma Fibroblast Growth Factor-21 Levels In Patients With Type 2 Diabetes Mellitus

Objective (1)To investigate the effects of glucose-lowering drugs such asinsulin,recombinant exendin-4 and rosiglitazone on plasma fibroblast growth factor-21 (FGF-21) levels in patients with type 2 diabetes mellitus(T2DM);(2) To investigate the effects of GLP-1 analogue on the gene and protein expressions of fibroblast growth factor-21(FGF-21) and its receptors in ApoE-/- Mice with Hypoadiponectinemia.Method (1) Plasma FGF-21 levels of new-onset T2DM patients,type 2 diabetic patients with poor glycemic control and sex-and age-matched normal controls were measured. The relationship between plasma FGF-21 levels and anthropometric and metabolic parameters was analyzed by SPSS;(2) ApoE-/-mice were randomly divided into four groups:high fat group (HF group),adenoviral pAd-U6-GFP (GF group),Liraglutide-adiponectin shRNA adenovirus co-injection group (HEA group) and adiponectin shRNA adenovirus injection group (ADI group) respectively. The gloucose-lipid metabolism basic biochemical indicators and insulin level in plasma were determined by enzymic or immunization methods. The mRNA expressions of adiponectin, FGF-21,β- klotho and FGFR1-4 were measured by quantitative real time PCR. The FGF-21 protein levels were determined by dot-blot.Results (1)Fasting plasma FGF-21 levels were higher in T2DM than in normal controls,after treatment with glucose-lowering drugs fasting plasma FGF-21 levels were decreased significantly. Linear correlation and multiple regression analysis showed WHR and blood glucose were related to plasma FGF-21 levels;(2) The adiponectin mRNA expressions of hepatic tissues and adipose tissues in ADI group were significantly decreased compared with two control groups; The FGF-21 mRNA expression of hepatic tissues in ADI group was significantly increased compared with two control groups; and in HEA group its expression was further increased, which has significantly statistics difference compared with ADI group. Theβ-klotho,FGFR1-3 mRNA expressions of hepatic tissues in ADI group were significantly decreased compared with control groups; and in HEA group their expressions were significantly increased compared with ADI group. The FGF-21 mRNA expression of adipose tissues in ADI group was significantly increased compared with control groups. Compared with control groups, adiponectin gene inhibition could down-regulated theβ-klotho, FGFR1 mRNA expressions. In HEA group,β-klotho, FGFR3 mRNA expressions were significantly increased compared with ADI group. The FGF-21 protein levels in liver, adipose tissues and plasma in ADI group were all increased compared with control groups; and in HEA group, it was further increased in plasma and liver compared with ADI group.Conclusion The change of plasma FGF-21 levels may be related to metabolic disturbance and insulin resistance,it might be a biology target of T2DM.