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

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

Research output: Contribution to journalArticle

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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 - 1983
Externally publishedYes

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Adipocytes
Adrenergic Agents
Rats
Insulin
Epidermal Growth Factor
Insulin Receptor
Isoproterenol
Adrenergic Agonists
Adrenergic Antagonists
Epidermal Growth Factor Receptor
Adrenergic Receptors
Alprenolol
IGF Type 2 Receptor
1-Methyl-3-isobutylxanthine
Bucladesine
Temperature
ErbB Receptors
rat Egfr protein
Washing
Cyclic AMP

ASJC Scopus subject areas

  • Biochemistry

Cite this

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.

β-Adrenergic regulation of insulin and epidermal growth factor receptors in rat adipocytes. / Pessin, Jeffrey E.; Gitomer, W.; Oka, Y.; Oppenheimer, C. L.; Czech, M. P.

In: Journal of Biological Chemistry, Vol. 258, No. 12, 1983, p. 7386-7394.

Research output: Contribution to journalArticle

Pessin, JE, Gitomer, W, Oka, Y, Oppenheimer, CL & Czech, MP 1983, 'β-Adrenergic regulation of insulin and epidermal growth factor receptors in rat adipocytes', Journal of Biological Chemistry, vol. 258, no. 12, pp. 7386-7394.
Pessin, Jeffrey E. ; Gitomer, W. ; Oka, Y. ; Oppenheimer, C. L. ; Czech, M. P. / β-Adrenergic regulation of insulin and epidermal growth factor receptors in rat adipocytes. In: Journal of Biological Chemistry. 1983 ; Vol. 258, No. 12. pp. 7386-7394.
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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.",
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