Role of alpha1A-adrenoceptor in the regulation of glucose uptake into white adipocyte of rats in vitro

Auton Neurosci. 2000 Nov 1;84(3):140-6. doi: 10.1016/s1566-0702(00)00197-1.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Agonists / pharmacology*
  • Adrenergic alpha-Antagonists / pharmacology*
  • Alkaloids
  • Animals
  • Benzophenanthridines
  • Biological Transport, Active / drug effects
  • Chromones / pharmacology
  • Clonidine / analogs & derivatives*
  • Clonidine / pharmacology
  • Deoxyglucose / metabolism
  • Dioxanes / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Estrenes / pharmacology
  • Glucose / metabolism*
  • Glucose Transporter Type 4
  • Indoles / pharmacology
  • Male
  • Maleimides / pharmacology
  • Methoxamine / pharmacology*
  • Monosaccharide Transport Proteins / metabolism*
  • Morpholines / pharmacology
  • Muscle Proteins*
  • Phenanthridines / pharmacology
  • Phosphoinositide-3 Kinase Inhibitors
  • Prazosin / pharmacology
  • Protein Kinase C / antagonists & inhibitors
  • Pyrrolidinones / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Sulfonamides / pharmacology
  • Tamsulosin
  • Type C Phospholipases / antagonists & inhibitors

Substances

  • Adra1a protein, rat
  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Alkaloids
  • Benzophenanthridines
  • Chromones
  • Dioxanes
  • Enzyme Inhibitors
  • Estrenes
  • Glucose Transporter Type 4
  • Indoles
  • Maleimides
  • Monosaccharide Transport Proteins
  • Morpholines
  • Muscle Proteins
  • Phenanthridines
  • Phosphoinositide-3 Kinase Inhibitors
  • Pyrrolidinones
  • Receptors, Adrenergic, alpha-1
  • Slc2a4 protein, rat
  • Sulfonamides
  • 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
  • U 73343
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • chlorethylclonidine
  • Deoxyglucose
  • chelerythrine
  • (2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane
  • Protein Kinase C
  • Type C Phospholipases
  • Tamsulosin
  • Methoxamine
  • Glucose
  • bisindolylmaleimide I
  • Clonidine
  • Prazosin