| Objective: Because of social economy developing,ingestion of high calorie especially refinement sugar and fat intaking,physical activity reduction and obesity, diabetes mellitus (DM) quickly becomes an epidemic disease in modern society. Insulin resistance (IR) is the basic pathologic physiology character of type 2 diabetes mellitus with complicated mechanism. Above all, diets take part in the development of IR. Animal experiments confirm long-term high sucrose or high fat diet to rat evoke IR. Then it is worth to study if there existed distinction among different source of high calorie ingestion. Tumor Necrosis Factorα(TNF-α)also play an important role in the development of IR. As main peripheral target organ of insulin, skeletal muscle can develop TNF-α,so it is very significance to investigate the relation between expression of TNF-αin skeletal muscle and insulin resistance as well as type 2 diabetes mellitus. This study is to feed SD female rat with high sucrose, high fat or high sucrose-high fat diet inducing insulin tresistance. After 4 weeks strptozotion(STZ,25mg/kg) was injected intrapenitoneallyto partly destructβcells inducing hyperglycemia. So a rat model of type 2 diabetes mellitus was set up, which may provide a particular advantage for investigating the relationship between the three different diets and insulin resistance, type 2 diabetes mellitus and the expression of TNFα mRNA in rat skeletal muscle.Method: The 48 rats were randomly assigned into four groups:the nomal control group(group C,n=12)fed with normal diet; experiment groups were high sucrose group(group HS, n=12), high fat group(group HF, n=12) and high sucrose-high fat group(group HSF, n=12) differently fed with high sucrose, high fat and high sucrose-high fat diet. Carbohydrate provided 80% calorie in high sucrose diet; fat provided 60% calorie in high fat diet which was rich in cooked lard; Carbohydrate and fat each provided 40% and 47% calorie in high sucrose-high fat diet. STZ (25mg/kg) was injected intrapenitoneally in 3 experiment groups after 4 weeks and all animals were put to death after 26 weeks. Body weight, fasting blood glucose, fasting serum insulin, serum triglyceride and cholestrol were observed after 4,8,26 weeks and calculated insulin sensitivity index(ISI). After 26 weeks and serum TNFαwas examined using RT-PCR and ELISA method. Moreover the correlation between ISI and serum triglyceride, cholestrol, the expression of TNFα mRNA in skeletal muscle and serum TNFαwere respectivelyanalyzed.Result: After 4 weeks, body weight, serum triglyceride and cholestrol increased in 3 experiment groups compared with those of group C; fasting serum insulin was much more than that of group C(p<0.01); as for fasting blood glucose there was no difference within 4 groups. ISI was reduced compared with group C(p<0.01)but there was no difference within 3 experiment groups(p>0.05). So obesity, hyperinsulinism, insulin resistance were induced and at the same level. After 8 weeks (4weeks behind STZ injected), all 3 experiment groups showed hyperglycemia (p<0.01); serum triglyceride and cholestrol were continuously higher then group C; the fasting serum insulin was same as group C；ISI was markedly reduced compared with group C(p<0.01) insulin resistance still existed but no diffrence among 3 groups. The rat model of type 2 diabetes mellitus had the characters of hyperlipidemia, hyperglycemia and insulin resistance. After 26 weeks (22 weeks behind STZ injected), one animal died in both group HS and group HF. Compared with group C, there was a significantly rising in 3 experiment groups in fasting blood glucose, serum triglyceride and cholestrol(p<0.01), the fasting serum insulin was still as same as that of group C. ISI was extraordinary lower than group C but no difference among 3 experiment groups. The level of serum TNFαin 3 experiment groups was much higher than that of groupC(p<0.05) and but there was no statistics difference among 3 groups (p>0.05). The expression of TNFαmRNA in 3 ex...
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