So far, the implications of GRK2 upregulation during HF have been exclusively considered for the detrimental effects on β AR signaling and cardiac inotropism (Koch et al., 1995), however, studies in non-cardiac cells have shown ability to interact with different substrates belonging to different cellular pathways such as insulin signaling, and, of note, to mediate insulin resistance produced by enhanced β2-AR receptor signaling (Cipolletta et al., 2009). This evidence concerns the gene INS and hydrops fetalis.