Ang(1-7) Improves Pancreatic Islets Function Via Upregulation Of ENOS Expression In Rats With High-fat Diet

ObjectiveTo investigate the effect of Ang(1-7) on pancreatic islet beta cell function and islet endothelial cell function in insulin-resistant rats fed with long-term high-fat diet.MethodsInsulin-resistant rat model was established by feeding high calorie and high-fat diet for 12 weeks and then was treated with Ang(1-7) (H1 group, n=15) at the dosage of 300ug/kg/d ih,for 4 weeks.Isulin sensitivity was assessed by euglycemic-hyperinsulinemic technique. Islet function was evaluated by Intra-vein insulin releasing test (IVIRT). The eNOS mRNA expression levels in the islets was detected by RT-PCR; The expression levels of eNOS in the islets were examined by immunohistochemistry; NO in the islets were examined by the method of Nitric acid reductase.ResultsCompared with normal control group (NC group, n=15), glucose infusion rate (GIR) in high-fat diet control group (H0 group, n=15) was reduced significantly {(5.19±0.81vs7.65±0.45)mg.kg-1.min-1 ,P<0.05}. the mRNA expression of eNOS and the protein expression of eNOS was reduced by 39.5% and48.3% respectively (all P<0.05); NO levels of Islet tissue decreased by 35.5% (P <0.05) . Compared with high-fat diet control group, insulin sensitivity of Ang(1-7) group (H1 group, n=15) was increased significantly with the curve of insulin secretion improved, the expression levels of eNOS mRNA increased by 26.9%; the expression levels of eNOS protein increased by 31.2%; insulin in the islets increased (P<0.05); NO levels of Islet tissue increased by 25.0% (P <0.05). ConclusionAng(1-7) improves pancreatic islet function siginificantly in rats fed with long-term high-fat diet. The mechanism may be via improving islet endothelial cell function.