Abstract
The number of cell-surface β-adrenergic receptors on cardiomyocytes isolated from diabetic rats, as determined by the hydrophilic ligand [3H] CGP-12177, decreased significantly to 59% of that in control rats (p<0.01), while the number of total cell β-adrenergic receptors, as determined by the hydrophobic ligand [125I] ICYP, did not differ between the two groups. Adenylate cyclase activity in cardiac plasma membrane isolated from diabetic rats also decreased significantly to 48% of the control level (p<0.05). Forty-eight hour in vivo insulin treatment improved the decrease in the number of cell-surface β-adrenergic receptors without causing any changes in serum T3 level or urinary catecholamine excretion rate. Insulin, high levels of glucose, and 3-hydroxybutyrate levels did not affect [3H] CGP-12177 binding to cardiomyocytes. Furthermore, diabetic cardiomyocytes showed significant (p<0.05) impairment in their recovery from agonist-induced down-regulation as compared with the control level.
These results indicate that the decrease in the number of β-adrenergic receptors in cardiac plasma membrane, which is associated with abnormalities in the receptor distribution, played an important role in the cardiac unresponsiveness to a β-adrenergic agonist in diabetic rats. The decrease in the number of receptors in plasma membrane is closely associated with the diabetic state and is reversed by short-term insulin treatment.
