Effects of theophylline on insulin receptors and insulin action in the adipocyte

The effects of theophylline on insulin receptors and insulin action in isolated rat adipocytes were studied. Theophylline reduced insulin binding by a decrease of receptor affinity. As concentration-response curves revealed, the effect was paralleled by a reduction of the cellular ATP content. Basal...

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Bibliographic Details
Published in:Molecular and cellular biochemistry 1983-01, Vol.57 (2), p.177-183
Main Authors: JOOST, H.-G, STEINFELDER, H.-J
Format: Article
Language:English
Subjects:
3-O-Methylglucose
Adenosine Triphosphate - metabolism
adipocytes
Adipose Tissue - drug effects
Adipose Tissue - metabolism
Animals
Biological and medical sciences
Biological Transport, Active - drug effects
Deoxyglucose - metabolism
Endocrine pancreas
Fundamental and applied biological sciences. Psychology
Hormones. Régulation
insulin
Insulin - analogs & derivatives
Insulin - metabolism
Insulin - pharmacology
Kinetics
Lipolysis - drug effects
Male
Methylglucosides - metabolism
Rats
Rats, Inbred Strains
Receptor, Insulin - drug effects
Receptor, Insulin - metabolism
theophylline
Theophylline - pharmacology
Vertebrates: endocrinology
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Summary:The effects of theophylline on insulin receptors and insulin action in isolated rat adipocytes were studied. Theophylline reduced insulin binding by a decrease of receptor affinity. As concentration-response curves revealed, the effect was paralleled by a reduction of the cellular ATP content. Basal as well as insulin-stimulated glucose transport (2-deoxyglucose and 3-O-methylglucose uptake) were inhibited by much smaller theophylline concentrations (0.15-0.6 mM) than those necessary to reduce insulin binding and to lower ATP levels (1-4.8 mM), or to stimulate lipolysis (0.3-2.4 mM). Insulin fully antagonized the effect of theophylline on lipolysis but failed to reverse the inhibition of glucose transport completely. The results suggest that (a) theophylline impairs insulin action at a post-receptor level and, at higher concentrations, by a decrease of receptor binding, (b) the reduction of insulin receptor affinity probably reflects ATP depletion of the adipocyte, and (c) the xanthine inhibits glucose transport independently from its effects on lipolysis.
ISSN:0300-8177
1573-4919
DOI:10.1007/BF00849194