title: beta-Adrenergic regulation of insulin and epidermal growth factor receptors in rat adipocytes.
abstract: Incubation of intact rat adipocytes with physiological concentrations of catecholamines inhibits the specific binding of 125I-insulin and 125I-epidermal growth factor (EGF) by 40 to 70%. Affinity labeling of the alpha subunit of the insulin receptor demonstrates that the inhibition of hormone binding is directly reflective of a specific decrease in the degree of receptor occupancy. The stereospecificity and dose dependency of the binding inhibitions are typical of a classic beta 1-adrenergic receptor response with half-maximal inhibition occurring at 10 nM R-(-)-isoproterenol. Specific alpha-adrenergic receptor agonists and beta-adrenergic receptor antagonists have no effect, while beta-adrenergic receptor antagonists block the inhibition of 125I-insulin and 125I-EGF binding to receptors induced by beta-adrenergic receptor agonists. Further, these effects are mimicked by incubation of adipocytes with dibutyryl cyclic AMP or with 3-isobutyl-1-methylxanthine. The beta-adrenergic inhibition of both 125I-insulin and 125I-EGF binding is very rapid, requiring only 10 min of isoproterenol pretreatment at 37 degrees C for a maximal effect. Removal of isoproterenol by washing the cells in the presence of alprenolol leads to complete reversal of these effects. The inhibition of 125I-EGF binding is temperature dependent whereas the inhibition of 125I-insulin binding is relatively insensitive to the temperature of isoproterenol pretreatment. Scatchard analysis of 125I-insulin and 125I-EGF binding demonstrated that the decrease of insulin receptor-binding activity may be due to a decrease in the apparent number of insulin receptors while the inhibition of EGF receptor binding can be accounted for by a decrease in apparent EGF receptor affinity. The decrease in the insulin receptor-binding activity is physiologically expressed as a dose-dependent decrease of insulin responsiveness in the adipocyte with respect to two known responses, stimulation of insulin-like growth factor II receptor binding and activation of the glucose-transport system. These results demonstrate a beta-adrenergic receptor-mediated cyclic AMP-dependent mechanism for the regulation of insulin and EGF receptors in the rat adipocyte.
mesh_terms: D019325:3-O-Methylglucose; D000273:Adipose Tissue / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002395:Catecholamines / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D066246:ErbB Receptors; D006728:Hormones / Q000494:pharmacology; D007328:Insulin / Q000031:analogs & derivatives / Q000378:metabolism; D007536:Isomerism; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D006728:Hormones; D007328:Insulin; D008757:Methylglucosides; D011956:Receptors, Cell Surface; C008147:insulin, iodo-; D019325:3-O-Methylglucose; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011972:Receptor, Insulin; D007545:Isoproterenol; D004837:Epinephrine