Sustained βAR Stimulation Mediates Cardiac Insulin Resistance in a PKA-Dependent Manner
| Autor: | Darawan Pinthong, Supachoke Mangmool, Sarawuth Phosri, Motohiro Nishida, Tsukasa Shimauchi, Tananat Denkaew, Warisara Parichatikanond |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment Glucose uptake Adrenergic beta-Antagonists Stimulation Mice 03 medical and health sciences Endocrinology Insulin resistance Internal medicine Receptors Adrenergic beta medicine Animals Humans Myocytes Cardiac Protein kinase A Molecular Biology Original Research Glucose Transporter Type 4 biology Myocardium Insulin Isoproterenol Glucose transporter General Medicine Adrenergic beta-Agonists medicine.disease Cyclic AMP-Dependent Protein Kinases Propranolol Rats HEK293 Cells 030104 developmental biology biology.protein Insulin Resistance Signal transduction GLUT4 Metoprolol Signal Transduction |
| Zdroj: | Molecular Endocrinology. 30:118-132 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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