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This Article Full Text Full Text (PDF) All Versions of this Article: 289/4/E627    most recent 00079.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Mulder, A. H. Articles by Bosch, R. R. Search for Related Content PubMed PubMed Citation Articles by Mulder, A. H. Articles by Bosch, R. R.

Adrenergic receptor stimulation attenuates insulin-stimulated glucose uptake in 3T3-L1 adipocytes by inhibiting GLUT4 translocation

¹Division of General Internal Medicine, Department of Medicine, Departments of ²Chemical Endocrinology,³Pharmacology and Toxicology, and ⁴Endocrinology, Radboud University Nijmegen Medical Centre, Nijmegen; and ⁵Department of Veterinary Pharmacy, Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Utrecht, Utrecht, The Netherlands

Submitted 19 February 2004 ; accepted in final form 23 May 2005

Activation of the sympathetic nervous system inhibits insulin-stimulated glucose uptake. However, the underlying mechanisms are incompletely understood. Therefore, we studied the effects of catecholamines on insulin-stimulated glucose uptake and insulin-stimulated translocation of GLUT4 to the plasma membrane in 3T3-L1 adipocytes. We found that epinephrine (1 µM) nearly halved insulin-stimulated 2-deoxyglucose uptake. The -adrenoceptor antagonist propranolol (0.3 µM) completely antagonized the inhibitory effect of epinephrine on insulin-stimulated glucose uptake, whereas the -adrenoceptor antagonist phentolamine (10 µM) had no effect. When norepinephrine was used instead of epinephrine, the results were identical. None of the individual selective -adrenoceptor antagonists (1 µM, ₁: metoprolol, ₂: ICI-118551, ₃: SR-59230A) could counteract the inhibitory effect of epinephrine. Combination of ICI-118551 and SR-59230A, as well as combination of all three selective -adrenoceptor antagonists, abolished the effect of epinephrine on insulin-stimulated glucose uptake. After differential centrifugation, we measured the amount of GLUT1 and GLUT4 in the plasma membrane and in intracellular vesicles by means of Western blotting. Both epinephrine and norepinephrine reduced insulin-stimulated GLUT4 translocation to the plasma membrane. These results show that -adrenergic (but not -adrenergic) stimulation inhibits insulin-induced glucose uptake in 3T3-L1 adipocytes, most likely via the ₂- and ₃-adrenoceptor by interfering with GLUT4 translocation from intracellular vesicles to the plasma membrane.

catecholamines; glucose transporter 4