REN and Insulin resistance: Significantly, systemic GRK2 inhibition during HF might be impressive because of its well-known positive cardiac effects and its ability to thwart the chronic activation of the renin–angiotensin–aldosterone (GRK2 inhibition could counteract phosphorylation and desensitization of Angiotensin II receptor type 1) and endothelin (GRK2 inhibition could prevent endothelin-induced insulin resistance) systems (Rockman et al., 1996; Zolk et al., 1999; Anavekar and Solomon, 2005; Usui et al., 2005).