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.
Sager
G
G
Department of Pharmacology, University of Tromsø, Norway.
Johansen
O
O
Mjøs
O D
OD
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000328:Adult; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D011412:Propanolamines / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D007328:Insulin; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; C033394:CGP 12177