Piperlonguminine Better Effect On The Improvement Of The Insulin Resistance In Rat

Objective:In this study,a high-fat diet was used to establish a rat model of insulin resistance(IR).At the same time,different concentrations of indole alkaloids(GBN)were given to intervene to observe the improvement effect of GBN on IR.The possible molecular mechanism of GBN to improve IR.Methods:1.High-fat diet and high-fat emulsions were used to intragastrically ensure caloric intake in rats.At the same time,different dosages of STZ and food-feeding models were explored.By comparing different ways of animal weight gain,fasting blood glucose and glucose tolerance,Finally choose the best model replication conditions.2.Rats were randomly divided into 6 groups.In addition to the normal group and the model group,rats given GBN were divided into three groups: low concentration,medium concentration,and high concentration(5 mg/kg,10 mg/kg,20 mg/kg)in different concentrations.Met(150 mg/kg)was administered.The kg)administration group was a positive control group.At the same time as the model was administered for 12 weeks,the body weight and fasting blood glucose of the rats were recorded and the glucose tolerance level was measured every 4 weeks.After 12 weeks,the rats were sacrificed,blood was collected and serum was used to measure serum total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL-C)and serum insulin biochemical indicators.3.After 12 weeks of modeling,rats were sacrificed and the muscles in the bones of the legs were removed and total protein was extracted.The protein expression of pAMPK,SIRT1,and PGC1-? was detected by western blot.4.After 12 weeks of modeling,rats were sacrificed and feces were taken.Measure the species richness and species composition of intestinal flora.Results:After 12 weeks of high-fat diet,fasting blood glucose levels,serum insulin levels,serum TC,TG,and LDL-C levels in the model group were significantly higher than those in the normal group,and the glucose tolerance was abnormal.The model was established successfully.Compared with the model group,GBN administration group improved fasting blood glucose,serum insulin levels,blood lipid levels and glucose tolerance.Compared with the normal group,the ratio of p-AMPK?/AMPK?,SIRT1,and PGC-1? protein expression in the model group were significantly lower.Compared with the model group,the ratio of p-AMPK?/AMPK? was increased in the GBN group.Up-regulation of p-AMPK?,SIRT1,and PGC-1? protein expression.Compared with the normal group,the species richness of the intestinal flora in the model group was significantly reduced,and the species richness of the three groups of rats administered with Suining was slightly increased,and the species richness of the intestinal flora was significantly increased in the metformin group reduce.