Long-term ethanol consumption decreases insulin-stimulated glucose uptake in isolated rat adipocytes. Here we investigate the mechanisms for this decrease. Male Wistar rats were fed for 4 weeks with a liquid diet containing 35% of the calories from ethanol and compared with pair-fed controls. Stimulation of 3-O-methylglucose transport in isolated adipocytes by insulin was decreased by 70% after ethanol feeding. However, stimulation by insulin of the tyrosine phosphorylation of the p85 subunit of phosphoinositide 3-kinase and the phosphorylation of Akt were not affected by ethanol feeding. GLUT4 was mobilized from intracellular light microsomes in response to insulin in both pair-fed and ethanol-fed rats, resulting in 4.3-fold and 3.3-fold increases in GLUT4 associated with plasma membrane in pair-fed and ethanol-fed rats respectively. Surface-accessible GLUT4, assessed by a trypsin cleavage assay or cell-surface labelling with bis-mannose photolabel, was increased 2.3-fold and 1.6-fold respectively, in pair-fed rats after treatment with insulin. In contrast, insulin did not increase surface-accessible GLUT4 in ethanol-fed rats. Treatment of adipocytes with R-phenylisopropyladenosine, an adenosine A1 receptor agonist, increased the transport of 3-O-methylglucose and trypsin-accessible GLUT4, in adipocytes from both pair-fed and ethanol-fed rats. These results demonstrate that whereas the insulin-mediated signalling and translocation of GLUT4 to the plasma membrane is maintained after ethanol feeding, the final fusion of GLUT4 vesicles to the plasma membrane is disrupted, preventing the stimulation of glucose uptake by insulin. Fusion of GLUT4 with the plasma membrane can be stimulated by the activation of adenosine A1 receptors.
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Research Article|
February 22 2001
GLUT4 vesicle trafficking in rat adipocytes after ethanol feeding: regulation by heterotrimeric G-proteins
Laurie A. POIRIER;
Laurie A. POIRIER
1Department of Nutrition, Room 201, Case Western Reserve University, 2123 Abington Road, Cleveland, OH 44106-4906, U.S.A.
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Nadia RACHDAOUI;
Nadia RACHDAOUI
1Department of Nutrition, Room 201, Case Western Reserve University, 2123 Abington Road, Cleveland, OH 44106-4906, U.S.A.
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Laura E. NAGY
Laura E. NAGY
1
1Department of Nutrition, Room 201, Case Western Reserve University, 2123 Abington Road, Cleveland, OH 44106-4906, U.S.A.
1To whom correspondence should be addressed (e-mail len2@po.cwru.edu).
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Publisher: Portland Press Ltd
Received:
June 28 2000
Revision Received:
November 06 2000
Accepted:
December 12 2000
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2001
2001
Biochem J (2001) 354 (2): 323–330.
Article history
Received:
June 28 2000
Revision Received:
November 06 2000
Accepted:
December 12 2000
Citation
Laurie A. POIRIER, Nadia RACHDAOUI, Laura E. NAGY; GLUT4 vesicle trafficking in rat adipocytes after ethanol feeding: regulation by heterotrimeric G-proteins. Biochem J 1 March 2001; 354 (2): 323–330. doi: https://doi.org/10.1042/bj3540323
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