ACEI Ameliorates Insulin Resistance And Glycometabolism In Rats Fed Long-term High-fat Diet And Induced With Streptozotocin

ObjectiveBlocking renin-angiotensin system (RAS)with angiotensin converting enzyme inhibitor (ACEI),observe the effects of rennin-angiotensin system blockade on mRNA expressions of PAI-1,Resistin and adiponectin in rats which were fed long-term high-fat diet and induced with streptozotocin, and investigate the correlation of renin-angiotensin system in adipose tissue region and insulin resistance (IR). Research the amelioration of blocking rennin-angiotensin system on insulin resistance, glycometabolism and its mechanism in these rats.MethodsTen rats which were randomly elected out from thirty male Wistar rats were taken as normal control (NC group, n=10), which were constantly fed common diet. And the rest—twenty rats were fed high-fat diet for 8 weeks. After 8 weeks, the twenty rats were randomly divided into high-fat diet fed group (HF group , N=10) and perindopril treated group (AE group, n=10).The two groups were still fed high-caloric and high-fat diet, and the AE group were intervened with perindopril 4mg/kg.d-1 for 12 weeks.Then two groups rats were given intraperitoneal injection of a small dose (20mg.kg-1) of streptozotocin (STZ). Insulin resistance and glycometabolism were assessed by oral glucose tolerance test(OGTT) and HOMA-IR after two weeks.Then the rats were sacrificed by decapitation,and adipocytes were islated from epididymal and perirenal adipose tissue for observing adipose cell morphous with HE dyeing and for mRNA expressions of PAI-1,Resistin and Adiponectin with reverse transcription- polymerase chain reaction(RT-PCR).ResultsAdipose cell in normal control group(NC group) was eumorphism and to line up in order.In OGTT,the fasting blood glucose was normal,the 30 minutes'blood glucose arrived the peak, the two hours'blood glucose all≤8.0mmol/L , each time-point blood glucose all≤11.1mmol/L.The HOMA-IR index all≤5.Compared with NC group, Adipose cell size increased and Adipose cell morphous appeared irregilar,viscera fat weight and viscera fat weight/body weight increased obviously, and the rats appeared abdominal fat in rats which were fed long-term high-fat diet and induced with streptozotocin .The fasting serum levels of blood glucose, free fatty acids and triglyeride increased obviously (all p<0.01). In HF group, AUC (area under curve ) of blood glucose and each time-point blood glucose of OGGT were higher ,HOMA-IR index was higher, the level of PAI-1 mRNA expressions had a 1.5 fold increase, the level of Resistin mRNA expressions had a 1.47 fold increase, and the level of Adiponectin mRNA expressions was decreased by 40.8% (all p<0.01).Compared with HF group, Adipose cell size was decreased and Adipose cell morphous appeared regilar,viscera fat weight and viscera fat weight/body weight were decreased obviously in AE group(p>0.05).The fasting serum levels of blood glucose, free fatty acids and triglyeride were decreased,but the difference was not significance (p>0.05).In AE group , AUC (area under curve ) of blood glucose and each time-point blood glucose of OGTT were lower, HOMA-IR index was lower. In AE group, the level of PAI-1 mRNA expressions was decreased by 28%, the level of Resistin mRNA expressions was decreased by 38.1%, and the level of Adiponectin mRNA expressions had a 1.62 fold increase (all p<0.05).ConclusionThese rats were induced by high fat high laboratory chow plus intraperitoneal injection of a small dose of streptozotocin,and appeared abdominal fat,glucose and lipid metabolic disorder, significant insulin resistance.The level of RAS, PAI-1 and Resistin mRNA expressions were increased, and the level of Adiponectin mRNA expressions was decreased in viscera adipose tissue.The ACEI drugs can ameliorate viscera fat, insulin resistance, glucose and lipid metabolic disorder through blocking the RAS. The mechanism can be correlated with ameliorating the expression of adipocytokine in viscera adipose tissue.