Hypoglycemic Effects And Expression Of Tnf-α Tgf-β1 Glut-4 And Ppar-γ Of Type 2 Diabetes Rats Influenced By Columbin

Objective: To observe the therapeuticle effect of Columbin on type 2 diabetic ratsinfer possible mechanism.Discuss the mechanism of action of relievation of insulinresistanceinfluencedbyColumbin.Methods: 2 groups were randomly devided in this experiment: healthy group andExperimental group. Rats in healthy group were fed of ordinary diet. The diabetic ratmodel was established by high fat diet 3 months and injection of streptozotocin(30mg/kg). Successful model was difined as non-free plasma glucose≥11.1mmol/L.Then model rats were randomizedly redivided into 4 groups: low-dose group(Columbin 25mg/kg), high-dose group (Columbin 50mg/kg), positive control groupand blank group. Normal group was given distilled water by intragastricadministration, the 4 experimental groups were given low-dose Columbin (25mg/kg),high-dose Columbin (50mg/kg), diformin(200mg/kg) and distilled water ,respectively. After 4 weeks administration, the whole groups would be put to deathby decapitation. Kidney tissue, perirenal fat, quadriceps femoris muscle tissue werereserved. Detected the expression of TNF-αin fat, TGF-β1 in kidney tissue by ELISA; while detected the expression of GLUT-4 mRNA in muscle, PPAR-γmRNAin fat by RT-PCR.Results and discussion: 1. After 3 months of high fat diet, the weight and Insulinwere increased significantly. After injection of streptozotocin, blood glucose of theexperimental group rats were increased significantly.2. The expression of inflammatory factor: The expression of TNF-αandTGF-β1 were significantly higher in control groups than in normal group, there wassignificant difference between the 2 groups(p<0.01). After therapy, in Columbingroups the expression of TNF-αand TGF-β1 were decreased in the order ofColumbin dose, high-dose group decreased the most , in which group the expressionof TNF-αand TGF-β1 were decreased 39.7% and 16.8% than in the control groups,respectively. While the diformin groups were descreased 48.1% and 19.1% than inthe control groups, respectively. There was significant difference between Columbingroups and control groups, Diformin groups and control groups, respectively(p<0.01), while there was no significant difference Columbin groups and normal groups,Diformin groups and normal groups, respectively(p>0.05); In the Columbinlow-dose group the expression of TNF-αwas decreased 21.7% than that in thecontrol groups, but there was no significant difference between the 2 groups(p>0.05); In the Columbin low-dose group the expression of TGF-β1 was decreased7.5% than that in the control groups, there was difference between the 2 groups(p<0.05).3.The expression of GLUT-4mRNA in muscle: The expression ofGLUT-4mRNA was significantly lower in control groups than in the normal group,there was significant difference between the 2 groups (p<0.01)After therapy, theexpression of GLUT-4mRNA in the Columbin high-dose group was increased 25%than in the control groups, respectively. Diformin group was increased 40.5% than in the control groups, respectively. There were both significant difference betweenColumbin groups and control groups, Diformin groups and control groups (p<0.01),while no significant difference between Columbin groups and normal groups,Diformin groups and normal groups. In the Columbin low-dose group the expressionof GLUT-4mRNA were increased than that in the control groups, but there was nosignificant difference between the 2 groups (p>0.05).4.The expression of PPAR-γmRNA in muscle: The expression of PPAR-γmRNAwas significantly lower in control groups than in the normal group, there wassignificant difference between the 2 groups (p<0.01)After therapy, the expression ofPPAR-γmRNA in the Columbin high-dose group was increased 22.2% than in thecontrol groups, respectively. Diformin group was increased 34.7% than in the controlgroups, respectively. There were both significant difference between Columbingroups and control groups, Diformin groups and control groups, (p<0.01), while nosignificant difference between Columbin groups and normal groups, Diformin groupsand normal groups. In the Columbin low-dose group the expression of PPAR-γmRNAwas increased 12.5% than in the control groups, there was difference betweenthe 2 groups(p<0.05).Conclusions: Columbin has the similar effect of reduce blood glucose with diformin,which were both dose dependent. High-dose Columbin could ameliorate the insulinresistance by the possible mechanism of exciting the receptor of PPAR-γ, to increasethe expression of GLUT-4 mRNA, accelerating the around tissue such as muscle, fatto transport and utilize glucose and restraining the expression of inflammatory factorincluding TNF-αand TGF-β1.