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Thrombin Stimulates Glucose Transport in Human Platelets via the Translocation of the Glucose Transporter GLUT-3 from α-Granules to the Cell Surface

Heijnen, Harry F.G., Oorschot, Viola, Sixma, Jan J., Slot, Jan W., James, David E.·1997·The Journal of Cell Biology
DOI 10.1083/jcb.138.2.323PMC PMC2138201
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Abstract

Increased energy metabolism in the circulating blood platelet plays an essential role in platelet plug formation and clot retraction. This increased energy consumption is mainly due to enhanced anaerobic consumption of glucose via the glycolytic pathway. The aim of the present study was to determine the role of glucose transport as a potential rate-limiting step for human platelet glucose metabolism. We measured in isolated platelet preparations the effect of thrombin and ADP activation, on glucose transport (2-deoxyglucose uptake), and the cellular distribution of the platelet glucose transporter (GLUT), GLUT-3. Thrombin (0.5 U/ml) caused a pronounced shape change and secretion of most α-granules within 10 min. During that time glucose transport increased approximately threefold, concomitant with a similar increase in expression of GLUT-3 on the plasma membrane as observed by immunocytochemistry. A major shift in GLUT-3 labeling was observed from the α-granule membranes in resting platelets to the plasma membrane after thrombin treatment. ADP induced shape change but no significant α-granule secretion. Accordingly, ADP-treated platelets showed no increased glucose transport and no increased GLUT-3 labeling on the plasma membrane. These studies suggest that, in human blood platelets, increased energy metabolism may be precisely coupled to the platelet activation response by means of the translocation of GLUT-3 by regulated secretion of α-granules. Observations in megakaryocytes and platelets freshly fixed from blood confirmed the predominant GLUT-3 localization in α-granules in the isolated cells, except that even less GLUT-3 is present at the plasma membrane in the circulating cells (∼15%), indicating that glucose uptake may be upregulated five to six times during in vivo activation of platelets.

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Research works printed but not linked: 34

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Metadata

Authors
Heijnen, H. F. G., Oorschot, V., Sixma, J. J., Slot, J. W., & James, D. E.
Affiliations
*Department of Hematology, University Hospital, 3508 GA Utrecht, The Netherlands; ‡Department of Cell Biology, Medical School, University of Utrecht, 3584 CX Utrecht, The Netherlands; and §Center for Molecular and Cellular Biology, University of Queensland, St. Lucia, Brisbane 4072, Australia
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
1997-07-28
Volume
138
Issue
2
Pages
323-330
ISSN
  • 0021-9525
  • 1540-8140
DOI
10.1083/jcb.138.2.323
PMC
PMC2138201
Cited by
77
References
0
Language
en

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