IRS1 and Insulin resistance: There are a few possible mechanisms underlying the improvement of insulin resistance by RAAS system blockers [15]: 1 Ang-II can increase serine phosphorylation of insulin receptor substrate-1 (IRS-1) and decrease the activity of IRS-1-associated phosphoinositide 3-kinase (PI3K), hindering insulin signal transduction, whereas RAAS blockers reverse this effect.