Prolonged stimulation of β 2 -adrenergic receptor with β 2 -agonists impairs insulin actions in H9c2 cells

• Published in: Journal of pharmacological sciences Vol. 138; no. 3; p. 184
• Main Authors: Parichatikanond, Warisara, Nishimura, Akiyuki, Nishida, Motohiro, Mangmool, Supachoke
• Format: Journal Article
• Language: English
• Published: Japan 01.11.2018
• Subjects: Adrenergic beta-2 Receptor Agonists - pharmacology; Albuterol - pharmacology; Cells, Cultured; Formoterol Fumarate - pharmacology; Glucose - metabolism; Glucose Transport Proteins, Facilitative - biosynthesis; Glucose Transporter Type 1 - biosynthesis; Glucose Transporter Type 4 - biosynthesis; Humans; Insulin - pharmacology; Insulin Antagonists - pharmacology; Insulin Resistance; Polymorphism, Genetic; Receptors, Adrenergic, beta-2 - metabolism; Salmeterol Xinafoate - pharmacology; βAR polymorphism; Glucose uptake; β-Agonist; GLUT translocation; Insulin resistance
• ISSN: 1347-8648

Insulin resistance is a condition in which there is a defect in insulin actions to induce glucose uptake into the cells. Overstimulation of β -adrenergic receptors (β ARs) is associated with the pathogenesis of insulin resistance in the heart. However, the mechanisms by which β -agonists affect insulin resistance in the heart are incompletely understood. The β -agonists are used for treatment of asthma due to bronchodilating effects. We also investigated the effects of β -agonists in human bronchial smooth muscle (HBSM) cells. In this study, we demonstrate that chronic treatment with salbutamol, salmeterol, and formoterol inhibited insulin-induced glucose uptake and GLUT4 synthesis in H9c2 myoblast cells. Sustained β AR stimulation also attenuated GLUT4 translocation to the plasma membrane, whereas short-term stimulation had no effect. In HBSM cells, prolonged treatment with β -agonists had no effect on insulin-induced glucose uptake and did not alter insulin-induced expressions of GLUT1, GLUT4, and GLUT10. In addition, genetic polymorphisms at amino acid positions 16 and 27 of β AR are linked to insulin resistance by significant suppression of GLUT4 translocation compared to wild-type. Thus, prolonged β AR stimulation by β -agonists impairs insulin actions through suppression of GLUT synthesis and translocation only in H9c2 cells.