Effect of Mas-receptor agonist administration on glucose utilization and skeletal muscle renin-angiotensin system in obese Zucker rats - role of NOX4 and p22phox

Abstract

Local renin-angiotensin system (RAS) in the skeletal muscle is of physiological relevance. Angiotesin 1-7 (Ang 1-7) is able to enhance insulin signalling and glucose transport activity in the skeletal muscle1. The major limitation of exogenous administration of Ang 1–7 is that it is a peptide, with a very short biological half-life. AVE0991, a non-peptide Mas-receptor agonist has been reported to mimic the action of Ang 1-72. The aim of our study was to evaluate the effect of AVE0991 application on the metabolic parameters, the expression of the RAS component and markers of oxidative stress in the skeletal muscle. 33-week-old male obese Zucker rats were treated with vehicle or AVE0991 (0.5mg/kg BW/day) via osmotic minipumps for two weeks. Gene expressions were determined in musculus quadriceps using qPCR analysis. AVE0991 treatment significantly improved glucose utilization, significantly enhanced the expression of renin receptor, transcription factor PLZF and NOX4, and had a tendency to increase the expression of p22phox. It has been shown that reactive oxygen species (ROS) have insulin-mimetic action in muscle3,4. Our data indicate that the improved glucose tolerance after AVE0991 treatment might occur - at least partially - due to enhanced ROS production in the skeletal muscle.