• MATHEMATICAL MODEL OF DIRECT RENIN INHIBITION IMPROVES SYSTEMIC INSULIN RESISTANCE AND SKELETAL MUSCLE GLUCOSE TRANSPORT BY B-S DISTRIBUTION

Abstract

Renin is the rate-limiting enzyme in renin-angiotensin system (RAS) activation. We sought to determine the impact of renin inhibition on whole-body insulin sensitivity and skeletalmuscle RAS, oxidative stress, insulin signaling, and glucose transport in the transgenic TG(mRen2)27 rat (Ren2),which manifests increased tissue RAS activity, elevated serum aldosterone, hypertension, and insulin resistance. Young (aged 6–9wk) Ren2 and age-matched Sprague Dawley control rats were treated with aliskiren[50mg/kg d, ip]orplacebofor 21dandadministeredanipglucose tolerance test. Insulin metabolic signaling and 2-deoxyglucose uptake in soleus muscle were examined in relation to tissue renin-angiotensin-aldosterone system [angiotensin (Ang) II, mineralocorticoid receptor (MR), and Ang type I receptor (AT1R)] and measures of oxidative stress as well as structural changes evaluated by light and transmission electronmicroscopy. The hazard rate function has been applied to the renin levels.