Inhibiting Insulin-Mediated β 2 -Adrenergic Receptor Activation Prevents Diabetes-Associated Cardiac Dysfunction
Authors' conclusion
These studies elucidate a novel mechanism by which hyperinsulinemia contributes to heart failure by increasing PDE4D expression and identify β2AR or GRK2 as plausible therapeutic targets for preventing or treating heart failure in subjects with type 2 DM.
Study context
- Population
- Mice with high-fat diet–induced obesity and diabetes mellitus (DM); human hearts with DM
- Comparison
- Inhibition of β2AR or GRK2 vs none in high-fat diet–fed mice
Main finding
As reported in the abstract
- High-fat diet selectively increases cardiac PDE4D expression, with reduced PKA phosphorylation of phospholamban, contributing to systolic and diastolic dysfunction
- PDE4D expression also elevated in human hearts with DM
- PDE4D induction mediated by insulin receptor, insulin receptor substrate, and GRK2/β-arrestin2-dependent transactivation of a β2AR–ERK signaling cascade
- Pharmacological inhibition of β2AR or GRK2, or genetic deletion of β2AR or β-arrestin2, significantly attenuate insulin-induced ERK phosphorylation and PDE4D induction, preventing DM-related contractile dysfunction
Original publication
Inhibiting Insulin-Mediated β 2 -Adrenergic Receptor Activation Prevents Diabetes-Associated Cardiac Dysfunction. Circulation. Published 4 November 2016. doi:10.
Summarised from the published abstract; every number is checked against it