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

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 (βARs) 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 βAR 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 βAR are linked to insulin resistance by significant suppression of GLUT4 translocation compared to wild-type. Thus， prolonged βAR stimulation by β-agonists impairs insulin actions through suppression of GLUT synthesis and translocation only in H9c2 cells.