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

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 plasm...

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Bibliographic Details
Published in:American journal of physiology: endocrinology and metabolism 2005-10, Vol.52 (4), p.E627-E633
Main Authors: MULDER, Alexandra H, TACK, Cees J, OLTHAAR, André J, SMITS, Paul, SWEEP, Fred C. G. J, BOSCH, Remko R
Format: Article
Language:English
Subjects:
Biological and medical sciences
Body fat
Cells
Fundamental and applied biological sciences. Psychology
Glucose
Hormones
Inhibitor drugs
Insulin
Vertebrates: endocrinology
Online Access:Get full text
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Summary: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 microM) nearly halved insulin-stimulated 2-deoxyglucose uptake. The beta-adrenoceptor antagonist propranolol (0.3 microM) completely antagonized the inhibitory effect of epinephrine on insulin-stimulated glucose uptake, whereas the beta-adrenoceptor antagonist phentolamine (10 microM) had no effect. When norepinephrine was used instead of epinephrine, the results were identical. None of the individual selective beta-adrenoceptor antagonists (1 microM, beta1: metoprolol, beta2: ICI-118551, beta3: SR-59230A) could counteract the inhibitory effect of epinephrine. Combination of ICI-118551 and SR-59230A, as well as combination of all three selective beta-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 beta-adrenergic (but not alpha-adrenergic) stimulation inhibits insulin-induced glucose uptake in 3T3-L1 adipocytes, most likely via the beta2- and beta3-adrenoceptor by interfering with GLUT4 translocation from intracellular vesicles to the plasma membrane. [PUBLICATION ABSTRACT]
ISSN:0193-1849
1522-1555