TY - JOUR
T1 - Sustained βAR stimulation mediates cardiac insulin resistance in a PKA-dependent manner
AU - Mangmool, Supachoke
AU - Denkaew, Tananat
AU - Phosri, Sarawuth
AU - Pinthong, Darawan
AU - Parichatikanond, Warisara
AU - Shimauchi, Tsukasa
AU - Nishida, Motohiro
N1 - Funding Information:
This work was supported by the National Science and Technology Development Agency Grant P-12-01409 (to S.M.) and in part by a grant from Naito Memorial Foundation and Daiko Foundation (M.N.). This work was also supported by the International Collaborative Research Program of National Institute for Physiological Sciences and Okazaki Institute for Integrative Bioscience.
Publisher Copyright:
© 2016 by the Endocrine Society.
PY - 2016/1
Y1 - 2016/1
N2 - 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.
AB - 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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U2 - 10.1210/me.2015-1201
DO - 10.1210/me.2015-1201
M3 - Article
C2 - 26652903
AN - SCOPUS:84953212764
SN - 0888-8809
VL - 30
SP - 118
EP - 132
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 1
ER -