Effects Of High Sucrose And High Fatty Acid Diets On The Expression Of GLUT4 MRNA In Skeletal Muscle Of Rats

Objective: With the development of social economy and the improvement of life level in recent years, the diets constitution of people has changed enormously. The morbidity rate of type 2 diabetes has been improved largely because of the high sucrose and high fatty acid diets and the less body activity or obesitas and so on. The popularity of type 2 diabetes is one of the main causes of morbidity and mortality worldwide besides tumor and cardiovascular disease. Insulin resistance is not only the main character of type 2 diabetes, but also the pathological and physiological foundation of hypertension, hyperlipemia, obesity and cardiovascular disease. With the new concept that diabetes is the glucolipid disease, some people believe that abnormality of lipid metabolism is probably the main pathological and physiological process of type 2 diabetes and its complications. And the study of the relation between free fatty acids and insulin resistance has been thought highly. The recent study indicates that the disturbance of glucose metabolism in skeletal muscle is the main appearance of insulin resistance. The glucose transporter 4 in the cell membrane mediates glucose intaking in peripheral tissue with insulin stimulus. The glucose transporter 4 is the main factor of glucose metabolism in muscle. And it is also the main target of insulin resistance. In our research, we fed male Wistar rats with high sucrose, high saturated fatty acid and high unsaturated fatty acid diets to observe the influence of the different diets on insulin resistance and the expression of GLUT4 mRNA in skeletal muscle, studying possible mechanism of insulin resistance induced by high sucrose, high saturated fatty acid and high unsaturated fatty acid diets.Method: 64 adult, healthy, clean, male Wistar rats, 16~20 weeks old, weight of 250g~300g, were purchased from experimental animal center in Hebei medical university and acclimatized for 2 weeks. Animals were randomly devided into normal control (NC) group, high sucrose (HS) group, high saturated fatty (HSF) group, high unsaturated fatty acid (HUF) group. Normal control group were fed with regular diets which constitute of calories from 65.5% for the carbohydrate, 10.3% for the fat, 24.2% for the protein. High sucrose group were fed with regular diets mixed 20% sucrose, the carbohydrate provided 76.5% calorie, the fat provided 7% calorie, the protein provided 16.5% calorie in it. High saturated fatty group and high unsaturated fatty acid group were fed regular diets mixed 20% butter, 20% soybean, the carbohydrate provided 43% calorie, the fat provided 41% calorie, the protein provided 16% calorie in them. The sucrose, soybean oil, butter all came from experimental animal center in Hebei medical university. Each proportion of unsaturated fatty acid and saturated fatty acids content is 84% and 16% in HUF group. The proportion of unsaturated fatty acid and saturated fatty acids content is 69.1% and 30.9% in HSF group. Pure degree of sucrose is 99%. Animals were fed for 24 weeks. Body weight (BW), systolic blood pressure (SBP), fasting blood glucose (FBG), serum total cholesterol (TC), serum triglyceride (TG), fasting serum insulin (FINS) were observed every 4 weeks and serum free fatty acids (FFA) was observed every 12 weeks during the 24-week feeding. Insulin resistance was evaluated by glucose infusion rate (GIR) of hyperinsulinemic euglycemic clamp technique after 24 weeks. And the content of GLUT4 mRNA in skeletal muscle was measured by polymerase chain reaction technique(RT-PCR). We study the correlation among the FBG, FFA, INS, GIR, TC, TG, BW and the content of GLUT4 mRNA in skeletal muscle.Result: 1. Body weight gain in HSF group, HUF group increased obviously, there were significant difference than that of in NC group(p<0.05 or p<0.01)after 12 weeks. Body weight gain in HS group didn't increase obviously, showed no difference between NC groups and HS group. At 24 week, Body weight in NC group, HS group, HSF group, HUF group increased 25.3%, 32.1%, 37.4%, 35.7% respectively. 2. FPG, TC, TG, INS in experimental groups all were much more than that in control group (p<0.05 or p<0.01). TC and TG in HSF group went up at the earlist stage, and there were no difference among experimental groups at 24 week. FBG and INS in experimental groups were significantly higher in control group from 8 weeks(p<0.05 or p<0.01), and there were no difference among the experimental groups. 3. FFA increased significantly in the three experimental groups compared with that in NC group after feeding for 12 weeks (p<0.01), FFA in HSF group obviously higher than that in HS and HUF group (p<0.01), the same results appeared at 24 week, but there was no difference among the experimental groups. 4. GIR was obviously lower in the experimental groups than that in NC group. From low to high, the consequence was HUF group, HSF group, HS group, NC group at 24 week. GIR in HUF group and HSF group was obviously lower than that in HS group (p<0.01 or p<0.01), and GIR in HUF group was a little lower than in HSF group but there was no significant difference. 5. The content of GLUT4 mRNA in skeletal muscle was markedly decreased in all experimental groups compared with the NC group. The content of GLUT4 mRNA in skeletal muscle in HSF group was a little lower than in HUF group, and that in HUF group was a little lower than in HS group, but there was no significant difference. 6. GIR was negatively correlated with BW, TG, GLU, FFA, INS. The content of GLUT4 mRNA in skeletal muscle was negatively correlated with FFA, FBG, INS and well positively correlated with GIR.Conclution: 1. Fed with high sucrose, high fat diets which were composed of different fatty acid after 24 weeks respectively, all the three experimental groups displayed hyperinsulinism, high fasting blood glucose, hypertension and low glucose infusion rate, so Wistar rats with insulin resistance and hypertension were induced successfully. 2. The content of GLUT4 mRNA in skeletal muscle was markedly decreased in rats fed with high sucrose and high fat diets. High free fatty acids in plasma may be the main mechanism. 3. Analysis of correlation clarified that the content of GLUT4 mRNA was negatively correlated with FFA, TC, INS, FBG and well positively correlated with GIR. These results suggested that the change of the content of GLUT4 mRNA was related closely with FFA, lipid and insulin resistance. 4. The research suggested that the content of GLUT4 mRNA would be decreased by high sucrose and high fat diets. And it might be the main mechanism of insulin resistance.