Intervation Of Anti-Diabetic Drugs On Ghrelin,Visfatin In Plasma And Tissue Of Type 2 Diabetic Rats

Objective:To measure the effects of insulin,metformin and pioglitazone on ghrelin and visfatin in fasting plasma and tissue of type 2 diabetic rats;to study the correlation between ghrelin and visfatin,and there relationships with the body weight,Lee index,visceral fat,serum glucose,insulin and blood lipid.To determine the correlations among ghrelin,visfatin and insulin sensitivity.Methods:50 6-week-age Wistar rats with body weight from 160 gram to 200 gram were randomly divided into two groups:normal control group received normal diet,and the diabetic group received high glucose and high fat diet.8 weeks later,the diabetic group rats were injected low dosage of streptozotocin(STZ 30mg/kg).48 hours later,the rats whose glucose more than 16.7mmol/L were diabetic rats.Then the diabetic rats were randomized into four groups:diabetic control group(DC), insulin-treatment group(INS),metformin-treatment group(MET)and pioglitazone-treatment group(PIO).8 weeks later,the fasting plasma ghrelin and visfatin were measured by enzyme-linked immunoassay(EIA).The body weight,body length and visceral fat weight were recorded,and the Lee index was calculated.The fasting blood glucose(FBG),triglyceride(TG),total cholesterol(YC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),fasting serum insulin(FINS)were measured in each subjects.Insulin sensitivity was estimated by Bennett Index.The expression levels of ghrelin in stomach and visfatin in visceral fat tissue were measured by immunohistochemistry.Results:1.The ghrelin levels of plasma and gastric tissue were significantly lower in DC group compared to NC group(P＜0.01).The ghrelin levels were higher in INS group compared to DC group,but there is no significance;the ghrelin levels in MET and PIO groups were significantly higher compared to DC group(P＜0.01).2.The visfatin levels of the plasma and visceral fat were significantly higher in DC group compared to the NC group(P＜0.01).The levels were lower in INS group compared to the DC group,but there is no significance;the levels were significantly lower in the MET and PIO groups compared to DC group(P＜0.05或P＜0.01).3.The plasma levels of ghrelin were negatively correlated with Lee index,visceral fat,FBG and FINS(r=-0.673,P＜0.001;r=-0.415,P=0.004;r=-0.228,P= 0.020;r=-0.427,P=0.004),positively correlated with ISI(r=-0.329,P=0.038) in the DC group.The plasma ghrelin in the MET group were negatively correlated with FINS(r=-0.265,P=0.011),and positively correlated with ISI(r=0.563,P =0.034).The plasma ghrelin in the PIO group were negatively correlated with FINS (r=-0.625,P=0.042),positively correlated with ISI(r=0.311,P=0.029).4.The plasma visfatin in the DC group and MET group were respectively positively correlated with visceral fat(r=0.722,P＜0.001;r=0.417,P=0.017)and FBG(r= 0.259,P=0.035;r=0.329,P=0.022),negatively correlated with HDL-C(r=-0.602,P=0.047;r=-0.113,P=0.039).The plasma visfatin in the INS and PIO groups were respectively positively correlated with visceral fat(r=0.499,P=0.031;r =0.175,P=0.036),and negatively correlated with HDL-C(r=-0.420,P=0.015;r =-0.453,P=0.028).5.The ghrelin levels in plasma were positively correlated with the levels in gastric tissue in each group.The visfatin levels in plasma were positively correlated with the levels in visceral fat in each of the five groups.6.There is no correlation between fasting plasma levels of ghrelin and visfatin.7.Multiple linear regression analysis showed that FINS and ISI were independent factors to the plasma levels of ghrelin in the DC,MET and PIO groups;the visceral fat were independent factors to the plasma levels of visfatin in all groups.Conclusion:The plasma levels of ghrelin were higher in the MET and PIO groups,and FINS and ISI were independent factors to plasma ghrelin.Metformin and pioglitazone maybe elevate ghrelin levels through improving insulin sensitivity.The plasma levels of visfatin were lower in the MET and PIO groups,and the visceral fat was the determinative factor.The research indicated that the visceral fat tissue was the mainly secreting tissue of visfatin,and the mechanism of metformin and pioglitazone reducing visfatin levels may due to the effect on reducing visceral fat.