Key result
Sustained β-adrenergic receptor stimulation mediates cardiac insulin resistance by reducing glucose uptake and GLUT4 expression via PKA-dependent pathways, which is antagonized by β-blockers.
Why the study?
Does sustained βAR stimulation induce cardiac insulin resistance via PKA-dependent pathways in cardiomyocytes?
Does sustained βAR stimulation induce cardiac insulin resistance via PKA-dependent pathways in cardiomyocytes?
Sustained βAR stimulation induces cardiac insulin resistance through a PKA-dependent pathway, which can be reversed by β-blockers.
Animal data leave open β-blocker effects on human cardiac insulin sensitivity; clinical studies required.
Insulin resistance is a condition in which cells are defective in response to the actions of insulin in tissue glucose uptake. Overstimulation of β-adrenergic receptors (βARs) leads to the development of heart failure and is associated with the pathogenesis of insulin resistance in the heart. However, the mechanisms by which sustained βAR stimulation affects insulin resistance in the heart are incompletely understood. In this study, we demonstrate that sustained βAR stimulation resulted in the inhibition of insulin-induced glucose uptake, and a reduction of insulin induced glucose transporter (GLUT)4 expression that were mediated by the β2AR subtype in cardiomyocytes and heart tissue. Overstimulation of β2AR inhibited the insulin-induced translocation of GLUT4 to the plasma membrane of cardiomyocytes. Additionally, βAR mediated cardiac insulin resistance by reducing glucose uptake and GLUT4 expression via the cAMP-dependent and protein kinase A-dependent pathways. Treatment with β-blockers, including propranolol and metoprolol antagonized isoproterenol-mediated insulin resistance in the heart. The data in this present study confirm a critical role for protein kinase A in βAR-mediated insulin resistance.
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Mangmool et al. (2015) studied Cardiac insulin resistance. Sustained βAR stimulation / β-blockers was evaluated on Insulin-induced glucose uptake and GLUT4 expression. Sustained β-adrenergic receptor stimulation mediates cardiac insulin resistance by reducing glucose uptake and GLUT4 expression via PKA-dependent pathways, which is antagonized by β-blockers.
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