阻断(前)肾素受体改善MSG大鼠胰岛素抵抗及其机制研究

项目名称： 阻断(前)肾素受体改善MSG大鼠胰岛素抵抗及其机制研究

项目编号： No.81200619

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 鄞国书

作者单位： 汕头大学

项目金额： 23万元

中文摘要： 近期研究显示前肾素-肾素-(前)肾素受体((P)RR）在胰岛素抵抗中有一定作用。我们证明MSG大鼠胰腺外分泌部及胰岛和白色脂肪的(P)RR表达量均明显增加。应用西格列汀干预MSG大鼠，改善胰岛素抵抗和β细胞功能的同时胰腺和脂肪的(P)RR表达均下调，提示(P)RR可能参与胰岛素抵抗的发生发展。本研究通过给予新生大鼠MSG皮下注射，断奶后给予高脂饮食，建立胰岛素抵抗合并β细胞缺陷的动物模型。通过给予该模型(P)RR抑制剂HRP，氯沙坦，安体舒通及联合用药，通过钳夹试验、脂肪及骨骼肌葡萄糖摄取率检测和OGTT分别评估系统、组织的胰岛素敏感性和β细胞功能，探讨胰腺、脂肪和骨骼肌局部RAS、氧化应激与炎症、胰岛素信号转导通路异常等在(P)RR阻断后改善糖代谢中的作用。从而证明阻断(P)RR能改善胰岛功能和胰岛素敏感性，且与氯沙坦和安体舒通存在一定协同作用。阻断(P)RR为胰岛素抵抗防治提供新靶点。

中文关键词： （前）肾素受体；胰岛；脂肪组织；胰岛素抵抗；MSG大鼠

英文摘要： Recent studies demostrated that prorenin-renin-(pro)renin receptor system may participate in the occurrence of insulin resistance, but the mechanisms are still unclear. We have testified that the quantity of (P)RR expression in pancreas including the exocrine area and islet and adipose tissue increased obviously in the MSG rat, and were down expression with sitagliptin treatment. The results suggested that (P)RR may play important role in the occurrence and development of insulin resistance. In this study, the rats with insulin resistance and β cell deficit were created by neonatally treated with MSG and given high-energy diet and then treated with handle region peptide (HRP), losartan and antisterone and combination. The system insulin resistance, insulin sensitivity of skeletal muscle and adipose tissue and functions of β cells of the animals were evaluated after 4 weeks treatment according to euglycemic byperinsulinemic clamp test, deoxyglucose uptake in vitro, and OGTT respectively. The possible mecannisms of improvement of glucose metabolism by blocking (P)RR including abnormal expression of tissue RAS, ativations of oxidative stress and imflamation, abnormal insulin signal transduction in the tissue of pancreat, adipose and skeletal muscle were investigated. This study will testify functions of β cells and

英文关键词： （Pro）renin receptor；islet；adipose tissue；insulin resistance；MSG rats