Adrenergic receptor stimulation attenuates insulin-stimulated glucose uptake in 3T3-L1 adipocytes by inhibiting GLUT4 translocation
Autor: | Remko R. Bosch, Alexandra H. Mulder, André J. Olthaar, Paul Smits, Cees J. Tack, Fred C.G.J. Sweep |
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Rok vydání: | 2005 |
Předmět: |
medicine.medical_specialty
Health aging / healthy living [IGMD 5] Monosaccharide Transport Proteins Adrenergic receptor Physiology Endocrinology Diabetes and Metabolism Glucose uptake Muscle Proteins Aetiology screening and detection [ONCOL 5] Vascular medicine and diabetes [UMCN 2.2] Propranolol Biology Mice Catecholamines Phentolamine Translational research [ONCOL 3] 3T3-L1 Cells Physiology (medical) Internal medicine Receptors Adrenergic beta Adipocytes medicine Animals Insulin Glucose Transporter Type 4 Cardiovascular diseases [NCEBP 14] Dose-Response Relationship Drug Endocrinology and reproduction [UMCN 5.2] Hormonal regulation [IGMD 6] Adrenergic beta-Agonists Protein Transport Glucose Epinephrine Endocrinology biology.protein Catecholamine GLUT1 GLUT4 medicine.drug |
Zdroj: | American Journal of Physiology : Endocrinology and Metabolism, 289, 4, pp. E627-33 American Journal of Physiology : Endocrinology and Metabolism, 289, E627-33 |
ISSN: | 1522-1555 0193-1849 |
DOI: | 10.1152/ajpendo.00079.2004 |
Popis: | Contains fulltext : 48697.pdf (Publisher’s version ) (Closed access) 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 alpha-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, beta(1): metoprolol, beta(2): ICI-118551, beta(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 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 beta(2)- and beta(3)-adrenoceptor by interfering with GLUT4 translocation from intracellular vesicles to the plasma membrane. |
Databáze: | OpenAIRE |
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