Insulin and β Adrenergic Receptor Signaling: Crosstalk in Heart

Recent advances show that insulin may affect beta adrenergic receptor (beta AR) signaling in the heart to modulate cardiac function in clinically relevant states, such as diabetes mellitus (DM) and heart failure (HF). Conversely, activation of beta AR regulates cardiac glucose uptake and promotes insulin resistance (IR) in HF. Here, we discuss the recent characterization of the interaction between the cardiac insulin receptor (InsR) and beta AR in the myocardium, in which insulin stimulation crosstalks with cardiac beta AR via InsR substrate (IRS)-dependent and G-protein receptor kinase 2 (GRK2)-mediated phosphorylation of beta(2)AR. The insulin-induced phosphorylation promotes beta(2)AR coupling to Gi and expression of phosphodiesterase 4D, which both inhibit cardiac adrenergic signaling and compromise cardiac contractile function. These recent developments could support new approaches for the effective prevention or treatment of obesity- or DM-related HF.