| Part I Rats of Insulin Resistance Model Induced by High-Fat-FedObjective:To establish insulin resistance rats model induced by high-fat-fed.Methods:60 male Wistar rats, eight-week-old, body weight 180-200g, were randomly divided into two groups:normal control group (n=12) and high-fat diet group (n=48). Normal diet group rats were fed with basic feed and high-fat diet group rats were fed with high-fat feed. Before and in the experiment, the body weight, fasting blood glucose and serum TC, TG, HDL-L and LDL-L levels were measured; the regulatory function of glucose metabolism determined by the glucose tolerance test and insulin tolerance test; serum insulin levels determined by enzyme-linked immuno-sorbent assay; insulin sensitivity evaluated by the insulin sensitivity index and insulin resistance index.Results:Compared with the normal diet group rats, the weight of high-fat diet group was improved obviously (P<0.01), the fasting blood glucose and HDL-c were no significant difference; the tolerance of glucose and insulin were impaired, the blood glucose levels after glucose load and glucose area under the curve were significantly higher than the normal diet group(P＜0.05 or P<0.01). Fasting serum insulin, insulin resistance index were significantly higher than the normal diet group (P＜0.05 or P＜0.01), and insulin sensitivity index was lower than the normal diet group (P<0.05).Conclusion:Insulin resistance obesity rats model can be successfully established by 9-week high-fat diet feeding. The model's characteristics is similar to human insulin resistance caused by obesity and we think it is a economic and practical animal model for the study of obesity and insulin resistance.Part II Effects of Ursolic Acid on Glucose, Lipid Metabolism and Glucokinase inInsulin Resistance RatsObjective:To observe the effects of ursolic acid on glucose, lipid metabolism and liver's glucokinase in insulin resistance rats.Methods:High-fat diet group (n=48) was randomly divided into four groups:model group (intragastric administration with PBS solution), metformin group (intragastric administration with metformin,200mg/kg-d), ursolic acid high-dose group (ursolic intragastric administration with ursolic acid,300mg/kg·d), and ursolic acid low-dose group (ursolic intragastric administration with ursolic acid,150mg/kg-d), each group was 12, and were fed with high-fat diet. Normal control group (intragastric administration with PBS solution), were fed with normal diet. At point 4 weeks and point 8 weeks after administration of each group, to observe the changes of weight, fasting blood glucose, fasting serum insulin, blood lipids, body weight, glucose tolerance, insulin tolerance, liver glycogen content and glucokinase; to calculate insulin sensitivity index and insulin resistance index; to observe the liver tissue pathological changes by light microscopy (HE staining); using enzyme-linked immuno-sorbent assay determined the content of glucokinase, RT-PCR assess the expression of glucokinase mRNA, Western Blot assess the expression of protein of glucokinase.Results:Ursolic acid and metformin treatment can lower body weight, and reduce TC, TG, LDL-C, workload glucose, glucose area under the curve, serum FINS, insulin resistance index in insulin resistance rats (P<0.05 or P<0.01), also they can increase insulin sensitivity index and content of glycogen (P<0.05 or P<0.01).The livers of drug groups partly close to normal, and model control group's livers obviously changed to fatty.Conclusion:Ursolic acid can reduce body weight, regulate glucose and lipid metabolism, increase the content of glycogen, glucokinase, the expression of glucokinase protein and mRNA to improve insulin resistance.
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