Opposite effects of insulin and catecholamines on LDL-receptor activity in human mononuclear leukocytes.
The mechanisms by which insulin and catecholamines affect low-density lipoprotein (LDL)-receptor activity were studied in freshly isolated human mononuclear leukocytes. Incubation of cells for up to 24 h in a lipid-free medium resulted in an increase in the specific binding, accumulation, and degradation of 125I-labeled LDL. Insulin stimulated the ability of the cells to bind, accumulate, and degrade the lipoprotein with high affinity, which may be caused by an increase in the LDL-receptor number without altering binding affinity. (-)-Epinephrine inhibited the specific binding, accumulation, and degradation of 125I-LDL. This effect appears to be mediated by a decrease in the number of LDL receptors and not by a change in the binding affinity. (-)-Norepinephrine, the unspecific beta-adrenergic agonist (-)-isoproterenol, and the beta 2-specific agonist terbutaline mimicked the effect of epinephrine on LDL-receptor activity. Catecholamines and beta-adrenergic agonists yielded sigmoidal log-concentration effect curves. The action of epinephrine was attenuated by the beta-antagonist (dl)-propranolol. These results demonstrate that insulin stimulates and catecholamines suppress the specific binding, accumulation, and degradation of 125I-LDL in human mononuclear leukocytes. The catecholamine action appears to be mediated by beta 2-adrenergic receptors. A suppression of LDL-receptor activity resulting from deficiency of insulin and elevated plasma catecholamine concentrations in uncontrolled insulin-dependent diabetic patients may contribute to the increased levels of LDL cholesterol observed in these patients.
Krone
W
W
Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Federal Republic of Germany.
Naegele
H
H
Behnke
B
B
Greten
H
H
D002395:Catecholamines / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D011973:Receptors, LDL / Q000187:drug effects* / Q000378:metabolism; D013726:Terbutaline / Q000494:pharmacology
D002395:Catecholamines; D007328:Insulin; D008077:Lipoproteins, LDL; D011943:Receptors, Adrenergic, beta; D011973:Receptors, LDL; D011433:Propranolol; D007545:Isoproterenol; D013726:Terbutaline; D009638:Norepinephrine; D004837:Epinephrine