Spironolactone Influences The Expression Of Adiponectin And PPARγ In Adipose Tissue Of Type 2 Diabetic Rats.

Objective: To investigate the effect of Spironolactone on the expression of adiponectin and PPARy mRNA in visceral adipose tissue of Streptozocin-treated type 2 diabetic rats,and Further to evaluate the effects of nonselective mineralocorticoid receptor(MR) blockade-Spironolactone in insulin resistance of type 2 diabetes.Methods:Sixty healthy male Sprague-Dawley(SD) rats were divided randomly into 2 groups:.Normal control rats (Group NC, n=15) were fed with routin animal feeds and experiment rats(n=45). The model of T2DM rats were established by fed with high-sucrose-high-fat diet for 8 weeks and then injected low dose Streptozotocin(STZ). The 29 diabetic rats were divided randomly into two subgroup:diabetes mellitus control group(group DM-C)and diabetic rats treated with Spironolactone (group DM-S).The group DM-C and DM-S rats were fed with the high-sucrose-high-fat diet. The group DM-S rats were treated with Spironolactone 40mg.kg-1.day"1 via intragastric administration while group DM-C and group NC were treated with corresponding distilled water for 8 weeks.Body mass(BM)and peripheral blood glucose of each group were tested every two weeks.The levels of serum triglyceride(TG).,total cholesterol(TC),fasting blood glucose(FBG), fasting insulin (FINS), hypokalemia and alodosterone were tested at the end of the experiment.The homeostatic model assessment for insulin resistance(HOMA-IR) was calculated.The expression levels of adiponectin mRNA, peroxisome proliferator activated receptor gamma (PPARy) mRNA and mineralocorticoid receptor mRNA in epididymal adipose tissue were detected by reverse transcription polymerse chain reaction(RT-PCR).Results:1) The levels of TC,TG,FBG and HOMA-IR were significantly higher in group DM-C and group DM-S compared with group NC at the end of the experiments(P<0.01). TG levels were lowered in group DM-S rats versus group DM-C rats(P<0.05) and other indictors had no statistical differences between the two groups. Compared with NC group, the aldosterone levels in group DM-C and group DM-S were increased (P<0.05),but there were no significant difference between in DM-S group and DM-C group.2) The homeostatic model assessment for insulin resistance(HOMA-IR) were were significantly higher in group DM-C and group DM-S compared with group NC at the end of the experiments(P<0.01).But there has no statistically difference between group DM-C and group DM-S (P>0.05).3) The expression levels of adiponectin mRNA, PPAR gamma mRNA and MR mRNA in epididymal adipose tissue. The mRNA levels of adiponection and PPAR gamma in group DM-C were lower than that in group NC and group DM-S (P<0.05),and there has no statistically difference between group DM-S and group NC(P> 0.05).MR mRNA expression in adipose tissue has no significant difference between the three groups(P>0.05).Conclusion: The plasma aldosterone level was increased in STZ-treated diabetic rats while the expression of adiponectin and PPARy mRNA in adipose tissue is decreased. Spironolactone increased the levels of adiponectin mRNA and PPARymRNA in adipose tissue and reduced serum TG levels of STZ-treated diabetic rats,which may represent a potential mechanism for protection against insulin resistance and target organ damage in diabetes.