Insulin and β Adrenergic Receptor Signaling: Crosstalk in Heart

Qin Fu, Qingtong Wang, Yang Kevin Xiang

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Recent advances show that insulin may affect β adrenergic receptor (βAR) signaling in the heart to modulate cardiac function in clinically relevant states, such as diabetes mellitus (DM) and heart failure (HF). Conversely, activation of βAR 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 βAR in the myocardium, in which insulin stimulation crosstalks with cardiac βAR via InsR substrate (IRS)-dependent and G-protein receptor kinase 2 (GRK2)-mediated phosphorylation of β2AR. The insulin-induced phosphorylation promotes β2AR 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. Insulin has bidirectional roles in cardiac metabolism and contractile function depending on the pathophysiological state.Chronic hyperinsulinemia impairs cardiac contractile function by inducing a Gi-biased β2AR signaling and upregulation of phosphodiesterase 4D (PDE4D) expression in the heart.Inhibition of β2AR is effective in rescuing cardiac dysfunction but not in preventing cardiac hypertrophy in diabetic mice.GRK2 acts as a node, linking insulin and βAR signaling in cardiac metabolism and cardiac contractile function, thus serving as a potential target for the treatment of DM-related HF.Early intervention by targeting the insulin-adrenergic signaling network may be effective in preventing cardiac complications in DM.

Original languageEnglish (US)
JournalTrends in Endocrinology and Metabolism
StateAccepted/In press - 2017

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


Dive into the research topics of 'Insulin and β Adrenergic Receptor Signaling: Crosstalk in Heart'. Together they form a unique fingerprint.

Cite this