Effects of insulin on mononuclear leukocyte beta-adrenoceptor density and adenylate cyclase coupling

The effects of insulin on human beta-adrenoceptor density and isoproterenol-induced cyclic AMP (cAMP) accumulation were characterized in mononuclear leukocytes from healthy subjects. In cells equilibrated with theophylline (4 mM) at 37 degrees C, insulin (4 microU/ml) was present in periods from 1 to 35 min prior to stimulation. The basal cAMP levels were not influenced. After 1 min pretreatment with insulin, the (-)-isoproterenol concentration necessary to cause half-maximal stimulation (EC50) decreased from 260 to 170 nM (P less than 0.025) and the maximal (-)-isoproterenol response above basal increased from 44 to 63 pmol/10(6) cells (P less than 0.01). The short exposure to insulin caused an increase in the number of functional beta-adrenoceptors from 1420 to 2160 receptors/cell (P less than 0.01). The increased (-)-isoproterenol responsiveness showed a time-dependent decline. When insulin had been present for 35 min before stimulation, the EC50 value had increased to 600 nM (P less than 0.01 vs. control) and the maximal (-)-isoproterenol response above basal was reduced to 29 pmol/10(6) cells (P less than 0.01 vs. control). The receptor density decreased to the pretreatment value (1480 receptors/cell) after 35 min exposure to insulin. The present study shows that insulin modifies the beta-adrenoceptor density as well as the beta-adrenoceptor coupling to adenylate cyclase, dependent on the duration of exposure.