| Objective:We had established type 2 diabetes animal model through long-term fed with high-fat diet to otsuka long-evans tokushima fatty (OLETF) rats. To explore:1. The prevention effect of type 2 diabetes of telmisartan, one of the Angiotensin II type 1 receptor blockers (ARB), and the effect of telmisartan on lipid metabolism and glycometabolism in OLETF rats fed with high-fat diet; 2.To observe the expression of monocyte chemoattractant protein-1 (MCP-1) in circulation and orchidic adipose tissue of OLETF rats; 3. To further observe the mechanisms for ameliorating insulin resistance and preventing diabetes of blocking renin angiotensin system and if through the MCP-1 passway.Methods:30 male OLETE rats and the fellow 12 male long-evans tokushima otsuka (LETO) non-diabetic rats which were 4 week old fed to adapt to environment 4 weeks. At eight weeks, the male OLETF rats began to be fed with high-fat diet, while the LETO rats were always fed with normal diet. To 22 weeks, check OGTT, diabetes did not happen in 42 rats. According to different treatment, the group respectively named:(1) telmisartan group (group T,5 mg·kg-1·d); (2) the metformin group (group M,100 mg·kg-1·d); (3) the high-fat diet group (group O); (4) normal control group (group NC). At the age of forty-eight weeks,80% of rats in group O had become diabetes. All rats were sacrificed after fasting for 12 hour, then separation serum and take orchidic adipose tissue.1. Rats vary in weight:body weight was observed every two weeks.2. Serum target:serum insulin were analyzed by ELISA, free fat acid, total cholesterol, triglycerides, low density level of apolipoprotein, high density level of apolipoprotein were measured by biochemistry, fasting blood glucose was analyzed by glucose oxidase method. Insulin resistance index= (FINS×FBG)/22.5. Serum MCP-1 was examined by ELISA.3. Expression levels of MCP-1:relative quantitative RT-PCR detected of MCP-1 mRNA; the expression levels of MCP-1 in adipose tissue were examined by Western Blotting.4. Correlation analysis:Compared the MCP-1 with free fatty acid, total cholesterol, triglycerides, low density level of apolipoprotein, high density level of apolipoprotein, fasting blood glucose and fasting insulin correlation between biochemical indicators. Results:1. Rats vary in weight:From the twentieth week, the weight of group O, group T and group M rats had obviously higher than group NC (P<0.01). The three groups had no obvious difference. Since 34 weeks, weight of group T had less than group O and group M, was not statistically significant (P respectively 0.312 and 0.415); 2. Data of lipid metabolism:In group O, the level of Serum free fatty acid, total cholesterol, low density level of apolipoprotein, fasting blood glucose and fasting insulin were significantly increased, meanwhile the insulin resistance index was higher (P respectively 0.001,0.043,0.000,0.000,0.023,0.000). The level of serum free fatty acid, total cholesterol, low density level of apolipoprotein and fasting insulin of group T were significantly lower then group O (P respectively 0.005,0.036, 0.000,0.036,0.029). Compared with the group M, free fatty acid, total cholesterol, fasting insulin and insulin resistance index of group T were lower (P respectively 0.000,0.047,0.017,0.008); 3. Morbidity of four groups:there were different of Morbidity in four groups (χ2=34.661, P=0.000), between group T and group M, there was a down tendency on morbidity, but no statistical significance (P=0.085). Group M were higher than group T (P=0.005).4. Circulation of MCP-1 level among groups: Compared with the group NC [(33.85±8.92)pg/ml], group O [(43.90±6.73)pg/ml] increased (P<0.05), the level of MCP-1 of group T [(34.64±7.60)pg/ml] and group M [(34.74±6.35)pg/ml]was lower than group O [(43.90±6.73) pg/ml] (P<0.05).5. MCP-1 mRNA:Compared with group NC, the MCP-1 mRNA was increased in group O (P=0.004); the level of MCP-1 mRNA of group T and group M were lower than group O (P respectively 0.006,0.003).6. Protein of MCP-1:The relative amounts protein of MCP-1 within adipose tissue in group O were higher than these in group NC (P=0.087). Compared with the group O, the relative amount protein of MCP-1 within adipose tissue was decreased in T and M group, but there was no statistical significance (P respectively 0.166 and 0.595).7. Correlation analysis: Linear correlation ananlysis showed that serum MCP-1 levels had positive relationship with the levels free fatty acid and insulin resistance index (r, P respectively 0.387,0.018; 0.609,0.000).Conclusion:1.We successfuliy established the type 2 diabetes animal models through long-term fed with high-fat die to OLETF rats. Weight, free fatty acid and low density level of apolipoprotein of OLETF rats significantly increased, rats had severe insulin resistance.2. The expression of MCP-1 in circulation and orchidic adipose tissue were conspicuous increased.3. After telmisartan treat, OLETF rats of free fatty acid, total cholesterol, fasting blood glucose and low density level of apolipoprotein in circulation were cut down and HOMA-IR was step down, indicated that telmisartan can ameliorate lipid metabolism and made fasting blood glucose decrease.4. Telmisartan reduced the expression of MCP-1 in circulation and orchidic adipose tissue and improved insulin resistance, made morbidity of diabetes decrease. Telmisartan may through inhibit the expression of MCP-1 to attenuate the insulin resistance in rats and prevent the morbidity of diabetes. |
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