title: Rat white adipocytes activate p85/p110 PI3K and induce PM GLUT4 in response to adrenoceptor agonists or aluminum fluoride.
abstract: Adipocyte responses to adrenergic and ß-adrenoceptor(-AR) (adrenoceptor) regulation are not sufficiently understood, and information helpful for elucidating the adrenoceptor-responsive machinery is insufficient. Here we show by using immunoprecipitated kinase analysis with a phosphatidylinositol 3-kinase (PI3K) p85 antibody that PI3K activation was induced by treatment with 10 or 100 µM norepinephrine (NE) for 15 min or with 10 mM aluminum fluoride (AF, a guanosine triphosphate (GTP)-binding (G) protein activator) for 20 min in white adipocytes (rat epididymal adipocytes) and that treatment with pertussis toxin (PTX, a G-protein inactivator) inhibited PI3K activation induced by the 20-min treatment with AF in the cells. In addition, western blot analysis revealed that glucose transporter 4 (GLUT4) level in the adipocyte plasma membrane (PM) fraction was increased by treatment with 10 µM NE, 100 µM dobutamine (DOB, a ß1-AR agonist), or 0.1 µM CL316243 (CL, a ß3-AR agonist) for 30 min or with 10 mM AF for 20 min. NE or AF treatment triggered 2-deoxyglucose (2-DG) uptake into adipocytes under the above conditions. Our results advance the understanding of responses to adrenoceptor regulation in white adipocytes and provide possible clues for clarifying the machinery involved in adrenergic and ß-AR responses in the cells.
authors.affiliation: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Chiba Institute of Science , Choshi , Japan.|Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University , Sapporo , Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohsaka
authors.affiliation: Yokohama College of Pharmacy, , Yokohama , Japan.|Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University , Sapporo , Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nomura
mesh_terms: D052438:Adipocytes, White / Q000187:drug effects* / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D004149:Dioxoles / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005459:Fluorides / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D017607:Aluminum Compounds; D004149:Dioxoles; D051275:Glucose Transporter Type 4; D011943:Receptors, Adrenergic, beta; C495694:Slc2a4 protein, rat; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D004280:Dobutamine; D058543:Class Ia Phosphatidylinositol 3-Kinase; D005459:Fluorides; D009638:Norepinephrine; C032311:aluminum fluoride
keywords: CL316243; aluminum fluoride; dobutamine; glucose transport; glucose transporter 4; norepinephrine; p85/p110; phosphatidylinositol 3-kinase; plasma membrane; white adipocytes