Advertisement

GLUT5 Expression and Fructose Transport in Human Skeletal Muscle

  • Harinder S. Hundal
  • Froogh Darakhshan
  • Søren Kristiansen
  • Stephen J. Blakemore
  • Erik A. Richter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 441)

Abstract

Biochemical and immunocytochemical studies have revealed that, in addition to GLUTI and GLUT4, human skeletal muscle also expresses the GLUT5 hexose transporter. The subcellular distribution of GLUT5 is distinct from that of GLUT4, being localised exclusively in the sarcolemmal membrane. The substrate selectivity of GLUT5 is also considered to be different to that of GLUTI and GLUT4 in that it operates primarily as a fructose transporter. Consistent with this suggestion studies in isolated human sarcolemmal vesicles have shown that fructose transport obeys saturable kinetics with a Vmax of 477 ± 37 pmol mg protein−1 min−1 and a Km of 8.3 ± 1.2 mM. Unlike glucose uptake, fructose transport in sarcolemmal vesicles was not inhibited by cytochalasin B suggesting that glucose and fructose are unlikely to share a common route of entry into human muscle. Muscle exercise, which stimulates glucose uptake through the increased translocation of GLUT4 to the plasma membrane, does not increase fructose transport or sarcolemmal GLUT5 content. In contrast, muscle inactivity, induced as a result of limb immobilisation, caused a significant reduction in muscle GLUT4 expression with no detectable effects on GLUT5. The presence of a fructose transporter in human muscle is compatible with studies showing that this tissue can utilise fructose for both glycolysis and glycogenesis. However, the full extent to which provision of fructose via GLUT5 is important in meeting the energy requirements of human muscle during both physiological and pathophysiological circumstances remains an issue requiring further investigation.

Keywords

Glucose Transporter Human Muscle Glut Expression Fructose Uptake Sarcolemmal Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Ahlborg, G. and O. Bjorkman. Splanchnic and muscle fructose metabolism during and after exercise. J. Appl. Physiol 69: 1244–1251, 1990.PubMedGoogle Scholar
  2. 2.
    Ahmed, A., J. N. A. Gibson, P. M. Taylor, and M. J. Rennie. Isolation of human skeletal muscle sarcolemmal vesicles for the investigation of glutamine transport. Biochem. Soc. Trans. 118: 1238–1239, 1990.Google Scholar
  3. 3.
    Baron, A. D., G. Brechtel, P. Wallace, and S. V. Edelman. Rates and tissue sites of non-insulin and insulin mediated glucose uptake in humans. Am. J. Physiol. 255: E769–E774, 1988.PubMedGoogle Scholar
  4. 4.
    Bell, G. I., T. Kayano, J. B. Buse, C. F. Burant, J. Takeda, D. Lin, H. Fukomoto, and S. Seino. Molecular biology of mammalian glucose transporters. Diabetes Care 13: 198–208, 1990.PubMedCrossRefGoogle Scholar
  5. 5.
    Blakemore, S. J., J. C. Aledo, J. James, F. C. Campbell, J. M. Lucocq, and H. S. Hundal. The GLUT5 hexose transporter is also localized to the basolateral membrane of the human jejunum. Biochem. J. 309: 7–12, 1995.PubMedGoogle Scholar
  6. 6.
    Blakemore, S. J., J. James, J. M. Lucocq, P. W. Watt, M. J. Rennie, and H. S. Hundal. Immunogold localization of the human fructose transporter (GLUT5) in human skeletal muscle. J. Physiol. 482: 19P, 1995. (Abstract)Google Scholar
  7. 7.
    Blakemore, S. J., P. K. Rickhuss, P. W. Watt, M. J. Rennie, and H. S. Hundal. Effects of limb immobilization on cytochrome c oxidase activity and GLUT4 and GLUT5 protein expression in human skeletal muscle. Clin. Sci. 91: 591–599, 1996.PubMedGoogle Scholar
  8. 8.
    Block, N. E., D. R. Menick, K. A. Robinson, and M. G. Buse. Effect of denervation on the expression of two glucose transporter isoforms in rat hindlimb muscle. J. Clin. Invest. 88: 1546–1552, 1991.PubMedCrossRefGoogle Scholar
  9. 9.
    Burant, C. F., J. Takeda, E. BrotLaroche, G. I. Bell, and N. O. Davidson. Fructose transporter in human spermatozoa and small intestine is GLUT5. J. Biol. Chem. 267: 14523–14526, 1992.PubMedGoogle Scholar
  10. 10.
    Coderre, L., K. V. Kandror, G. Vallega, and P. F. Pilch. Identification and characterization of an exercise-sensitive pool of glucose transporters in skeletal-muscle. J. Biol. Chem. 270: 27584–27588, 1995.PubMedCrossRefGoogle Scholar
  11. 11.
    Davidson, N. O., A. M. L. Hausman, C. A. Ifkovits, J. B. Buse, G. W. Gould, C. F. Burant, and G. I. Bell. Human intestinal glucose transporter expression and localization of GLUT5. Am. J. Physiol. 262: C795–C800, 1992.PubMedGoogle Scholar
  12. 12.
    Douen, A. G., T. Ramlal, S. Rastogi, P. J. Bilan, G. D. Cartee, M. Vranic, J. O. Holloszy, and A. Klip. Exercise induces recruitment of the “insulin-responsive glucose transporter”. J. Biol. Chem. 265: 13427–13430, 1990.PubMedGoogle Scholar
  13. 13.
    Goodyear, L. J., M. F. Hirshman, and E. S. Horton. Exercise-induced translocation of skeletal muscle glucose transporters. Am. J. Physiol. 261: E795–E799, 1991.PubMedGoogle Scholar
  14. 14.
    Gould, G. W. and G. D. Holman. The glucose transporter family:structure, function and tissue specific expression. Biochem. J. 295: 329–341, 1993.PubMedGoogle Scholar
  15. 15.
    Guma, A., J. R. Zierath, H. Wallberg-Henriksson, and A. Klip. Insulin induces translocation of glut-4 glucose transporters in human skeletal-muscle. Am. J. Physiol. 31: E613–E622, 1995.Google Scholar
  16. 16.
    Handberg, A., L. Kayser, P. E. Hoyer, and J. Vinten. A substantial part of GLUTI in crude membranes from muscle originates from perineurial sheaths. Am. J. Physiol. 262: E721–E727, 1992.PubMedGoogle Scholar
  17. 17.
    Henriksen, E. J., K. J. Rodnick, C. E. Mondon, D. E. James, and J. O. Holloszy. Effect of denervation or unweighting on GLUT-4 protein in rat soleus muscle. J. Appl. Physiol. 70: 2322–2327, 1991.PubMedCrossRefGoogle Scholar
  18. 18.
    Holman, G. D. and S. W. Cushman. Subcellular localization and trafficking of the GLUT4 glucose transporter isoform in insulin-responsive cells. BioEssays 11: 753–759, 1994.CrossRefGoogle Scholar
  19. 19.
    Hundal, H. S., A. Ahmed, A. Guma, Y. Mitsumoto, A. Marette, M. J. Rennie, and A. Klip. Biochemical and immunocytochemical localization of the “GLUT5 glucose transporter” in human skeletal muscle. Biochem. J. 286: 348–353, 1992.Google Scholar
  20. 20.
    Hundal, H. S., D. L. Maxwell, A. Ahmed, F. Darakhshan, Y. Mitsumoto, and A. Klip. Subcellular distribution and immunocytochemical localization of Na, K-ATPase subunit isoforms in human skeletal muscle. Mol. Memb. Biol. 11: 255–262, 1994.CrossRefGoogle Scholar
  21. 21.
    Kayano, T., C. F. Burant, H. Fukumoto, G. W. Gould, Y. Fan, R. L. Eddy, M. G. Byers, T. B. Shows, S. Seino, and G. I. Bell. Human facilitative glucose transporters: Isolation, functional characterization, and gene localization of cDNAs encoding an isoform (GLUT5) expressed in small intestine, kidney, muscle, and adipose tissue an unusual glucose transporter pseudogene-like sequence (GLUT6). J. Biol. Chem. 265: 13276–13282, 1990.PubMedGoogle Scholar
  22. 22.
    Kristiansen, S., F. Darakhshan, E. A. Richter, and H. S. Hundal. Fructose transport and GLUT5 protein in human sarcolemmal vesicles. Am. J. Physiol. 273: E543–E548, 1997.PubMedGoogle Scholar
  23. 23.
    Kristiansen, S., M. Hargreaves, and E. A. Richter. Exercise-induced increase in glucose transport, GLUT4 and VAMP-2 in plasma membrane from human muscle. Am. J. Physiol. 270: E197–E201, 1996.PubMedGoogle Scholar
  24. 24.
    Kristiansen, S., M. Hargreaves, and E. A. Richter. Progressive increase in glucose transport and GLUT4 in human sarcolemmal vesicles during moderate dynamic exercise. Am. J. Physiol. 272: E385–E389, 1997.PubMedGoogle Scholar
  25. 25.
    Mantych, G. J., D. E. James, and S. U. Devasker. Jejunal/Kidney glucose transporter isoform (GLUT-5) is expressed in the human blood-brain barrier. Endocrinology 132: 35–40, 1993.PubMedCrossRefGoogle Scholar
  26. 26.
    Marette, A., E. Burdett, A. Douen, M. Vranic, and A. Klip. Insulin induces the translocation of glut4 from a unique intracellular organelle to transverse tubules in rat skeletal-muscle. Diabetes 41: 1562–1569, 1992.PubMedCrossRefGoogle Scholar
  27. 27.
    Marette, A., E. Burdett, A. G. Douen, M. Vranic, and A. Klip. Insulin stimulates the translocation of GLUT4 glucose transporters from a unique intracellular organelle to both the plasma membrane and transverse tubules in rat skeletal muscle. Diabetes 41: 1562–1569, 1992.PubMedCrossRefGoogle Scholar
  28. 28.
    Marette, A., J. M. Richardson, T. Ramlal, T. W. Balon, M. Vranic, J. E. Pessin, and A. Klip. Abundance, localization and insulin-induced translocation of glucose transporters in red and white muscle. Am. J. Physiol. 263: C443–C452, 1992.PubMedGoogle Scholar
  29. 29.
    Mueckler, M. Facilitative glucose transporters. Eur. J. Biochem. 219: 713–725, 1994.PubMedCrossRefGoogle Scholar
  30. 30.
    Pilegaard, H., C. Juel, and F. Wibrand. Lactate transport studied in sarcolemmal giant vesicles from rats: effect of training. Am. J. Physiol. 254: E156–E160, 1993.Google Scholar
  31. 31.
    Rand, E. B., A. M. Depaoli, N. O. Davidson, G. I. Bell, and C. F. Burant. Sequence, tissue distribution, and functional characterization of the rat fructose transporter GLUT5. Am. J. Physiol. 264: Gl169–G1176, 1993.Google Scholar
  32. 32.
    Roy, D., A. Marette, E. Burdett, A. Douen, M. Vranic, and A. Klip. Exercise induces the translocation of glut4 to transverse tubules from an intracellular pool in rat skeletal-muscle. Biochem. Biophys. Res. Comm. 41: 1515–1562, 1992.Google Scholar
  33. 33.
    Shepard, P. R., E. M. Gibbs, C. Wesslau, G. W. Gould, and B. B. Kahn. Small intestine glucose transporter (GLUT5) is present in human muscle, adipocytes and brain: Biochemical characterization and translocation. Diabetes 41: 1360–1365, 1992.CrossRefGoogle Scholar
  34. 34.
    Wright, E. M., J. R. Hirsch, D. D. F. Loo, and G. A. Zampighi. Regulation of Na+/glucose cotransporters. J. Expt. Biol. 200: 287–293, 1997.Google Scholar
  35. 35.
    Wright, E. M., D. D. F. Loo, E. Turk, and B. A. Hirayama. Sodium cotransporters. Curr. Opin. Cell Biol. 8: 468–473, 1996.PubMedCrossRefGoogle Scholar
  36. 36.
    Zierath, J. R., L. A. Nolte, E. Wahlstrom, D. Galuska, P. R. Shepherd, B. B. Kahn, and H. Wallberghenriksson. Carrier-mediated fructose uptake significantly contributes to carbohydrate-metabolism in human skeletal-muscle. Biochem. J. 311: 517–521, 1995.PubMedGoogle Scholar
  37. 37.
    Zorzano, A., P. Munoz, M. Camps, C. Mora, X. Testar, and M. Palacin. Insulin-induced redistribution of GLUT4 glucose carriers in the muscle fiber: In search of GLUT4 trafficking pathways. Diabetes 45 (Suppl. 1): S70–S81, 1996.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Harinder S. Hundal
    • 1
  • Froogh Darakhshan
    • 1
  • Søren Kristiansen
    • 2
  • Stephen J. Blakemore
    • 1
  • Erik A. Richter
    • 2
  1. 1.Department of Anatomy and PhysiologyThe University of DundeeDundeeScotland
  2. 2.Copenhagen Muscle Research CentreAugust Krogh Institute, University of CopenhagenDenmark

Personalised recommendations