Mechanism Study On Insulin Resistance And Therapy In High-Fat-Fed Rats

OBJECTIVE:To explore the pathogenesis of IR , we established a rat model of insulin resistance(IR) by feeding high-fat diet for 8 weeks and measured serum insulin, leptin, tumor necrosis factor- a (TNF- a ) concentrations and the expression of the lipogenic transcription factor, sterol regulatory element binding protein-Ic (SREBP-lc) in liver of rats. We administered different drugs to high-fat-fed rats for 6 weeks and measured relative hormone in serum and SREBP -Ic mRNA expression in liver of rats at the baseline and at the end point in order to evaluate the effects of these drugs and reveal their therapy mechanisms. METHODS:1. We established a rat model of IR by feeding Wistar rats with high-fat diet for 8 weeks.2. Randomly divided the high-fat-fed rats into four groups: the high-fat-feeding-8-weeks group in which rats were killed immediately, the model control group that were fed with high-fat diet for another 6 weeks, the rosiglitazone group that were fed with high-fat diet and rosiglitazone(3mg/kg/d) for 6 weeks, the jinqijiangtangpian group that were fed with high-fat diet and jinqijiangtangpian (2.1g/kg/d) for 6 weeks.3. We measured blood glucose, serum insulin and lipid concentrations in rats at the baseline and at the end point.4. We measured serum leptin, serum TNF- a level and the expression of SREBP-lc mRNA in liver of these rats.RESULTS1.Compared with control, rats fed with high-fat diet had significantly higherweight, fat, fat/weigh, blood glucose, serum insulin concentration, serum lipidand lower ISI.2.Compared with control, high-fat-fed rats had significantly higher serum leptin,serum TNF- a and higher expression level of SREBP-lc in liver. 3.There were no significant difference in weight and FBG between the two groups that were treated with rosiglitazone or jinqijiangtangpian. Treatment with drugs reduced fasting insulin, OGTT 2h glucose, serum lipid and increased ISI in high-fat-fed rats.4. Treatment with rosiglitazone or jinqijiangtangpian reduced serum leptin and TNF- a concentrations and decreased the expression of SREBP-lc mRNA in liver in high-fat-fed rats.5 There was a positive correlation between serum leptin concentration and weight, fat, fat/weight, fasting insulin concentration, serum triacylglycerol concentration, free fatty acids(FFA) concentration, serum TNF- a concentration while there was a negative correlation between serum leptin concentration and ISI. 6.There was a positive correlation between serum TNF- a concentration and fat, fat/weight, fasting insulin concentration, serum triacylglycerol, FFA concentration and leptin concentration while there was a negative correlation between serum TNF- a. concentration and ISI. CONCLUSIONS:1 .A rat model of IR can be established by feeding high-fat diet. 2.The mechanisms of IR might exist linking dyslipidemia, hyperleptinemia, high serum TNF- a and overexpression of SREBP-lc mRNA.3.Rosiglitozone can improve IR and dyslipidemia by affecting leptin, TNF- a and overexpression of SREBP-1 c mRNA.4.Jinqijiangtangpian has the similar effects with rosiglitozone and the mechanisms might be that it could affect leptin, TNF- a and expression of SREBP-lc mRNA, too.