| Objective:To investigate the serum visfatin and VCAM-1 levels in insulin resistance rats induced by high fat diet, analysis the correlation among serum visfatin,VCAM-1 and insulin resistance. The expression of visceral adipose tissue visfatin mRNA was assessed by RT-PCR. The effect of rosiglitazone on visfatin and VCAM-1 was examined. To explore the possible mechanism of visfatin effect on insulin resistance and diabetes.Methods : Total 50 clean male Wistar rats weighed 280～320 grams were randomly divided into two groups:there were 20 rats in normal control group (NC), and 30 rats in high-fat-fed group (HF) group. The rats in NC group were fed with standard rat chow, containing 10.3% fat, 24.2% protein, and 65.5% carbohydrate as percentage of total calories, and the total calories was 348 kcal per 100g rat chow;The rats in HF group were fed with isocaloric high fat diet ,containing 59.8% fat, 20.1% protein and 20.1% carbohydrate as a percentage of total calories, the total calories was 501 kcal of per 100g rat chow. Body weight was observed every week. Four weeks later, 10 rats were chosen randomly from each group. After fasted for 10 hours, the rats were taken blood sample from endocanthion venous plexus; the serum was separated for the detection of insulin, Hyperinsulin aemiceuglycaemic clamp was performed on these rats to confirm that the insulin resistant rat model was duplicated successfully. After this procedure, the rest 20 rats in HF group were divided randomly into high fat control group (HC), rosiglitazone group(RSG),there were 10 rats in each group. All of the rats were maintained original diets, but the rats in RSG group were given Rosiglitazone 3 mg·kg-1·d-1 orally. The rats in NC and HC group were given sodium chloride orally, once per day, and the volume was the same with the RSG group. The intervention lasted for 8 weeks. Body weight was observed once a week, and the dosage was regulated according to the body weight. After 8 weeks of intervention, the blood sample was taken from endocanthion venous plexus; serum was separated for the detection of lipid, insulin, visfatin, VCAM-1, insulin and free fatty acid. The concentration of visfatin, VCAM-1 was determined by ELISA, the serum FFA level was measured by copper-chromogenic technology. The hyperinsulin aemiceugly- caemic clamp was carried out to detect the change of GIR in different groups. After the clamp, the rats were sacrificed by depletion, the adipose pad around kidneys and epididymides was weighed exactly, the renal or epididymal adipose pad were removed and flash-frozen in liquid nitrogen, then stored at -70°C for further detections. The expression of visceral adipose tissue visfatin mRNA was assessed by RT-PCR. Data was collected and analyzed through t test or analysis of variance. The statistic software was SPSS13.0, Differences with P values <0.05 were considered significant.Results:1 After four-week high fat feeding, the body weight of HF group rats was higher than that of NC group, but there was no statistic difference between the two groups (P>0.05). The fasting blood glucose, fasting insulin in HF group rats increased remarkably, there were significant differences compared with the NC group (P<0.01).The GIR in HF group rats decreased remarkably, there were significant differences compared with the NC group (P<0.01).2 After twelfth -week high fat feeding, The serum TC,TG, FFA,FBG in HC group rats increased remarkably, there were significant differences compared with the NC group (P<0.05). The FINS level increased remarkably, there were significant differences compared with the NC group (P<0.01). The GIR in HF group rats decreased remarkably, there were significant differences compared with the NC group (P<0.05).3 After twelfth -week high fat feeding, the body weight of HC group rats was higher than that of NC group, but there was no statistic difference between the two groups (P>0.05). But the weight of visceral adipose tissue of HC group rats was higher than that of NC group, there were significant differences (P<0.01). The serum visfatin, VCAM-1 in HC group rats increased remarkably, there were significant differences compared with the NC group (P<0.01,P<0.05).4 The serum TC,TG,FBG in RSG group rats was lower than HC group , and the GIR was higher than HC group , there were significant differences (P<0.05). The FINS and FFA of HF group rats decreased remarkably, there were significant differences compared with the NC group (P<0.01).5 The serum VCAM-1 in RSG group rats was lower than HC group, there were significant difference (P<0.01).There was no statistic difference of visfatin between RSG group and HC group (P>0.05). The weight of visceral adipose tissue of RSG group rats was higher than that of HC group, there were significant differences (P<0.01).6 The visfain expressive level in visceral adipose tissue of HC and RSG groups was significantly higher than that of NC group (P<0.05).There was no significantly difference of the visfatin expressive level in visceral adipose tissue between HC group and RSG group. (P>0.05).7 The correlation analysis show that: the serum visfatin level was positively correlated with VCAM-1 ( r=0.910, P<0.01),TC (r=0.367 P<0.05),TG(r=0.499, P<0.01),visceral adipose tissue (r=0.446,P<0.05).After multiple regression analysis, the visfatin levels seemed to be the best variable in predicting VCAM-1 levels (r=0.828,P<0.01).Conclusion :1 The high-fat-fed rats had higher level of serum FINS and FBG. The GIR was decreased significant in high-fat-fed group. It demonstrated that the insulin resistance rats model was successfully induced by 4-week high fat diet.2 The high-fat-fed rats had higher level of serum visfatin and VCAM-1,and the visfatin expressive level in visceral adipose tissue was higher , visfatin and VCAM-1 may play important roles in the develop of insulin resistance.3 The RSG decreased the serum FINS, FBG, TC, TG, FFA level in high-fat-fed rats, increased the GIR. These results suggested that the RSG could ameliorate the insulin resistant state in high-fat-fed rats. RSG may inhibit the production of VCAM-1,and play a role in the prevention and treatment of vascular complications led by insulin resistance .but the visfatin was not regulated by RSG, there may be other pathways that visfatin contribute to insulin resistance.4 the serum visfatin level was positively correlated with VCAM-1,visfatin levels seemed to be the best variable in predicting VCAM-1 levels. visfatin may play an important role in the development of T2DM vascular complications.
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