Publication: Sustained βAR stimulation mediates cardiac insulin resistance in a PKA-dependent manner
Issued Date
2016-01-01
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ISSN
19449917
08888809
08888809
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2-s2.0-84953212764
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Mahidol University
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SCOPUS
Bibliographic Citation
Molecular Endocrinology. Vol.30, No.1 (2016), 118-132
Suggested Citation
Supachoke Mangmool, Tananat Denkaew, Sarawuth Phosri, Darawan Pinthong, Warisara Parichatikanond, Tsukasa Shimauchi, Motohiro Nishida Sustained βAR stimulation mediates cardiac insulin resistance in a PKA-dependent manner. Molecular Endocrinology. Vol.30, No.1 (2016), 118-132. doi:10.1210/me.2015-1201 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/43239
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Title
Sustained βAR stimulation mediates cardiac insulin resistance in a PKA-dependent manner
Other Contributor(s)
Department of Pharmacology and Center of Excellence for Innovation in Drug Design and Discovery
Mahidol University
National Institutes of Natural Sciences - National Institute for Physiological Sciences
Kyushu University
Precursory Research for Embryonic Science and Technology
Japan Science and Technology Agency
Mahidol University
National Institutes of Natural Sciences - National Institute for Physiological Sciences
Kyushu University
Precursory Research for Embryonic Science and Technology
Japan Science and Technology Agency
Abstract
© 2016 by the Endocrine Society. 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.