Abstract
In an attempt to know the functional role of alpha1A-adrenoceptors in adipose tissue, white adipocytes (WAT) of Wistar rats were used to investigate the change of glucose uptake after pharmacological activation of alpha1-adrenoceptors. Methoxamine enhanced the uptake of radioactive glucose into isolated WAT in a concentration-dependent manner. Translocation of glucose transporter (GLUT4) from cytosol to membrane was also stimulated with methoxamine. Action of methoxamine to raise glucose uptake was abolished in WAT pre-incubated with the antagonists, both tamsulosin and WB 4101, at concentrations sufficient to block alpha1A-adrenoceptors. However, chlorethylclonidine (CEC). the antagonist of alpha1B-adrenoceptors, showed the inhibition of methoxamine-induced action only at a higher concentration. Even under the treatment with maximal concentration of CEC, methoxamine can produce action about 80% of the vehicle-treated control. The major role of alpha1A-adrenoceptors in the stimulation of glucose uptake by methoxamine can thus be considered. In the presence of specific inhibitor of phospholipase C (PLC), U73312, methoxamine-stimulated glucose uptake into WAT was reduced in a concentration-dependent manner and U73343, the negative control of U73312, did not affect the action of methoxamine. Moreover, chelerythrine and GF 109203X diminished the methoxamine-stimulated glucose uptake at a concentration sufficient to inhibit protein kinase C (PKC). Inhibition of phosphoinositide-3 kinase (PI-3 kinase) by LY294002 also abolished methoxamine-stimulated glucose uptake. Therefore. the obtained data suggest that an activation of alpha1A-adrenoceptors, presence in WAT, by agonist and/or neurotransmitter may increase the glucose uptake via PLC-PKC pathway and the activation of PI-3 kinase.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adipocytes / drug effects
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Adipocytes / metabolism*
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Adrenergic alpha-1 Receptor Agonists
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Adrenergic alpha-1 Receptor Antagonists
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Adrenergic alpha-Agonists / pharmacology*
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Adrenergic alpha-Antagonists / pharmacology*
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Alkaloids
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Animals
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Benzophenanthridines
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Biological Transport, Active / drug effects
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Chromones / pharmacology
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Clonidine / analogs & derivatives*
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Clonidine / pharmacology
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Deoxyglucose / metabolism
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Dioxanes / pharmacology
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Enzyme Inhibitors / pharmacology
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Estrenes / pharmacology
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Glucose / metabolism*
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Glucose Transporter Type 4
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Indoles / pharmacology
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Male
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Maleimides / pharmacology
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Methoxamine / pharmacology*
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Monosaccharide Transport Proteins / metabolism*
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Morpholines / pharmacology
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Muscle Proteins*
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Phenanthridines / pharmacology
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Phosphoinositide-3 Kinase Inhibitors
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Prazosin / pharmacology
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Protein Kinase C / antagonists & inhibitors
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Pyrrolidinones / pharmacology
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Rats
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Rats, Wistar
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Receptors, Adrenergic, alpha-1 / physiology*
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Sulfonamides / pharmacology
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Tamsulosin
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Type C Phospholipases / antagonists & inhibitors
Substances
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Adra1a protein, rat
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Adrenergic alpha-1 Receptor Agonists
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Adrenergic alpha-1 Receptor Antagonists
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Adrenergic alpha-Agonists
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Adrenergic alpha-Antagonists
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Alkaloids
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Benzophenanthridines
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Chromones
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Dioxanes
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Enzyme Inhibitors
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Estrenes
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Glucose Transporter Type 4
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Indoles
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Maleimides
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Monosaccharide Transport Proteins
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Morpholines
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Muscle Proteins
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Phenanthridines
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Phosphoinositide-3 Kinase Inhibitors
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Pyrrolidinones
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Receptors, Adrenergic, alpha-1
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Slc2a4 protein, rat
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Sulfonamides
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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U 73343
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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chlorethylclonidine
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Deoxyglucose
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chelerythrine
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(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
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Protein Kinase C
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Type C Phospholipases
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Tamsulosin
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Methoxamine
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Glucose
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bisindolylmaleimide I
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Clonidine
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Prazosin