Effects of angiotensin II AT1 receptor inhibition and exercise training on insulin action in rats on high-fat diet

Aim: This study was to determine whether combination of the angiotensin II AT1 receptor blocker (ARB), candesartan cilexetil, and exercise training can prevent the development of high-fat diet-induced insulin resistance. Main methods: F344/NSlc rats were fed normal chow diet or high-fat (HF) diet for 7 weeks. The HF-fed rats were either administered candesartan cilexetil (5 mg.kg(-1) day(-1)). exercise-trained, or received a combination of these 2 treatments. Key findings: Oral glucose tolerance tests (OGTT) showed that combined treatment with candesartan cilexetil and exercise increased glucose tolerance as compared with each treatment alone in HF-fed rats. Moreover, euglycemic-hyperinsulinemic clamp analysis showed improvement in glucose infusion rate with exercise training or candesartan cilexetil treatment alone, and further improvement was observed with the combination treatment. Systolic blood pressure improved with candesartan cilexetil but not with exercise alone. Finally, Glut-4 protein expression in soleus muscle was decreased with HF diet, and the expression was increased by exercise and not candesartan cilexetil treatment. Significance: These results suggest that the combination of candesartan cilexetil and exercise training improves insulin resistance as compared with each treatment alone. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.