β-Adrenergic regulation of insulin and epidermal growth factor receptors in rat adipocytes

J. E. Pessin, W. Gitomer, Y. Oka, C. L. Oppenheimer, M. P. Czech

Research output: Contribution to journalArticle

93 Scopus citations

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 α 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 β1-adrenergic receptor response with half-maximal inhibition occurring at 10 nM R-(-)-isoproterenol. Specific α-adrenergic receptor agonists and β-adrenergic receptor antagonists have no effect, while β-adrenergic receptor antagonists block the inhibition of 125I-insulin and 125I-EGF binding to receptors induced by β-adrenergic receptor agonists. Further, these effects are mimicked by incubation of adipocytes with dibutyryl cyclic AMP or with 3-isobutyl-1-methylxanthine. The β-adrenergic inhibition of both 125I-insulin and 125I-EGF binding is very rapid, requiring only 10 min of isoproterenol pretreatment at 37°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 β-adrenergic receptor-mediated cyclic AMP-dependent mechanism for the regulation of insulin and EGF receptors in the rat adipocyte.

Original languageEnglish (US)
Pages (from-to)7386-7394
Number of pages9
JournalJournal of Biological Chemistry
Volume258
Issue number12
StatePublished - Dec 1 1983
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Pessin, J. E., Gitomer, W., Oka, Y., Oppenheimer, C. L., & Czech, M. P. (1983). β-Adrenergic regulation of insulin and epidermal growth factor receptors in rat adipocytes. Journal of Biological Chemistry, 258(12), 7386-7394.