Biochemical Genetics

, Volume 43, Issue 3–4, pp 175–187 | Cite as

Glucose Transporter 1, Distribution in the Brain and in Neural Disorders: Its Relationship With Transport of Neuroactive Drugs Through the Blood-Brain Barrier

Article

Abstract

Facilitative glucose transport is mediated by one or more of the members of the closely related glucose transporter (GLUT) family. Thirteen members of the GLUT family have been described thus far. GLUT1 is a widely expressed isoform that provides many cells with their basic glucose requirement. It is also the primary transporter across the blood-brain barrier. This review describes the distribution and expression of GLUT1 in brain in different pathophysiological conditions including Alzheimer’s disease, epilepsy, ischemia, or traumatic brain injury. Recent investigations show that GLUT1 mediates the transport of some neuroactive drugs, such as glycosylated neuropeptides, low molecular weight heparin, and d-glucose derivatives, across the blood-brain barrier as a delivery system. By utilizing such highly specific transport mechanisms, it should be possible to establish strategies to regulate the entry of candidate drugs.

Keywords:

glucose transporter distribution in brain expression in brain disease neuroactive drug saccharide blood-brain barrier 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Au, K. K., Liong, E., Li, J. Y., Li, P. S., Liew, C. C., Kwok, T. T., Choy, Y. M., Lee, C. Y., and Fung, K. P. (1997). Increases in mRNA levels of glucose transporters types 1 and 3 in Ehrlich ascites tumor cells during tumor development. J. Cell Biochem. 67:131–135.PubMedGoogle Scholar
  2. Bergsneider, M., Hovda, D. A., Shalmon, E., Kelly, D. F., Vespa, P. M., Martin, N. A., Phelps, M. E., McArthur, D. L., Caron, M. J., Kraus, J. F., and Becker, D. P. (1997). Cerebral hyperglycolysis following severe traumatic brain injury in humans: A positron emission tomography study. J. Neurosurg. 86:241–251.PubMedCrossRefGoogle Scholar
  3. Bilsky, E. J., Egleton, R. D., Mitchell, S. A., Palian, M. M., Davis, P., huber, J. D., Jones, H., Yamamura, H. I., Janders, J., Davis, T. P., Porreca, F., Hruby, V. J., and Polt, R. (2000). Enkephalin glycopeptide analogues produce analgesia with reduced dependence liability. J. Med. Chem. 43:2586– 2590.PubMedGoogle Scholar
  4. Boado, R. J. (1998a). Molecular regulation of the blood-brain barrier GLUT 1 glucose transporter by brain-derived factors. J. Neural. Transm. Suppl. 53:323–331.Google Scholar
  5. Boado, R. J. (1998b). Brain-derived peptides increase blood-brain barrier GLUT1 glucose transporter gene expression via mRNA stabilization. Neurosci. Lett. 255:147–150.Google Scholar
  6. Bolz, S., Farrell, C. L., Dietz, K., and Wolburg, H. (1996). Subcellular distribution of glucose transporter (GLUT-1) during development of the blood-brain barrier in rats. Cell Tissue Res. 284:355-365.PubMedGoogle Scholar
  7. Bourasset, F., Cisternino, S., Temsamani, J., and Scherrmann, J. M. (2003). Evidence for an active transport of morphine-6-β-d-glucuronide but not P-glycoprotein-mediated at the blood-brain barrier. J. Neurochem. 86:1564–1567.PubMedGoogle Scholar
  8. Chavez, J. C., and LaManna, J. C. (2002). Activation of hypoxia-inducible factor-1 in the rat cerebral cortex after transient global ischemia: Potential role of insulin-like growth factor-1. J. Neurosci. 22:8922–8931.PubMedGoogle Scholar
  9. Cheng, C. M., Cohen, M., Wang, J., and Bondy, C. A. (2001). Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex. FASEB J. 15:907–915.PubMedGoogle Scholar
  10. Cornford, E. M., Gee, M. N., Swartz, B. E., Mandelkern, M. A., Blahd, W. H., Landaw, E. M., and Delgado-Escueta, A. V. (1998a). Dynamic [18F]fluorodeoxyglucose positron emission tomography and hypometabolic zones in seizures: Reduced capillary influx. Ann. Neurol. 43:801-808.Google Scholar
  11. Cornford, E. M., Hyman, S., Black, K. L., Cornford, M. E., Vinters, H. V., and Pardridge, W. M. (1995). High expression of the Glut1 glucose transporter in human brain hemangioblastoma endothelium. J. Neuropathol. Exp. Neurol. 54:842–851.PubMedGoogle Scholar
  12. Cornford, E. M., Hyman, S., Cornford, M. E., and Caron, M. J. (1996). Glut1 glucose transporter activity in human brain injury. J. Neurotrauma 13:523–536.CrossRefPubMedGoogle Scholar
  13. Cornford, E. M., Hyman, S., Cornford, M. E., Landaw, E. M., and Delgado-Escueta, A. V. (1998b). Interictal seizure resections show two configurations of endothelial GLUT1 glucose transporter in the human blood-brain barrier. J. Cereb. Blood Flow Metab. 18:26–42.Google Scholar
  14. Cornford, E. M., Hyman, S., and Pardridge, W. M. (1993). An electron microscopic immunogold analysis of developmental up-regulation of the blood-brain barrier GLUT1 glucose transporter. J. Cereb. Blood Flow Metab. 13:841–854.PubMedGoogle Scholar
  15. Doege, H., Bocianski, A., Scheepers, A., Axer, H., Eckel, J., Joost, H. G., and Schürmann, A. (2001). Characterization of glucose transporter 10 (GLUT10), a novel heart and skeletal muscle-specific sugar transport facilitator. Diabetes 50(Suppl 2):A277–A278.Google Scholar
  16. Doege, H., Schürmann, A., Bahrenberg, G., Brauers, A., and Joost, H. G. (2000). GLUT8, a novel member of the sugar transport facilitator family with glucose transport activity. J. Biol. Chem. 275:16275–16280.PubMedGoogle Scholar
  17. Egleton, R. D., and Davis, T. P. (1997). Bioavailability and transport of peptides and peptide drugs into the brain. Peptides 18:1431–1439.PubMedGoogle Scholar
  18. Egleton, R. D., Mitchell, S. A., Huber, J. D., Janders, J., Stropova, D., Polt, R., Yamamura, H. I., Hruby, V. J., and Davis, T. P. (2000). Improved bioavailability to the brain of glycosylated met-enkephalin analogs. Brain Res. 881:37–46.PubMedGoogle Scholar
  19. Farrell, C. L., and Pardridge, W. M. (1991). Blood-brain barrier glucose transporter is asymmetrically distributed on brain capillary endothelial lumenal and ablumenal membranes: An electron microscopic immunogold study. Proc. Natl. Acad. Sci. U.S.A. 88:5779–5783.PubMedGoogle Scholar
  20. Filira, F., Biondi, L., Cavaggion, F., Scolaro, B., and Rocchi, R. (1990). Synthesis of O-glycosylated tuftsins by utilizing threonine derivatives containing an unprotected monosaccharide moiety. Int. J. Pept. Protein Res. 36:86–96.PubMedCrossRefGoogle Scholar
  21. Halmos, T., Santarromana, M., Antonakis, K., and Scherman, D. (1997). Synthesis of O-methylsulfonyl derivatives of D-glucose as potential alkylating agents for targeted drug delivery to the brain: Evaluation of their interaction with the human erythrocyte Glut1 hexose transporter. Carbohyd. Res. 299:15–21.Google Scholar
  22. Hamlin, G. P., Cernak, I., Wixey, J. A., and Vink, R. (2001). Increased expression of neuronal glucose transporter 3 but not glial glucose transporter 1 following severe diffuse traumatic brain injury in rats. J. Neurotrauma 18:1011–1018.PubMedGoogle Scholar
  23. Harr, S. D., Simonian, N. A., and Hyman, B. T. (1995). Functional alterations in Alzheimer’s disease: Decreased glucose transporter 3 immunoreactivity in the perforant pathway terminal zone. J. Neuropathol. Exp. Neurol. 54:38–41.PubMedGoogle Scholar
  24. Horvat, S., Horvat, J., Varga-Defterdarovic, L., Pavelic, K., Chung, N. N., and Schiller, P. W. (1993). Methionine-enkephalin related glycoconjugates: Synthesis and biological activity. Int. J. Pept. Protein Res. 41:399–404.PubMedCrossRefGoogle Scholar
  25. Janigro, D. (1999). Blood-brain barrier, ion homeostasis, and epilepsy: Possible implications towards the understanding of ketogenic diet mechanisms. Epilepsy Res. 37:223–232.PubMedGoogle Scholar
  26. Joost, H. G., Doege, H., Bocianski, A., and Schürmann, A. (2001). Erratum: Nomenclature of the GLUT family of sugar transport facilitators, GLUT6, GLUT9, GLUT10, and Glut11. Biochem. J. 358:791–792.Google Scholar
  27. Joost, H. G., and Thorens, B. (2001). The extended GLUT family of sugar/polyol transport facilitators: Nomenclature, sequence characteristics, and potential function of its novel members. Mol. Membr. Bio. 18:247–256.Google Scholar
  28. Kayano, T., Burant, C. F., Fukumoto, H., Gould, G. M., Fan, Y.-S., Eddy, R. L., Byers, M. G., Shows, T. B., Seino, S., and Bell, G. I. (1990). 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 and an unusual glucose transporter pseudogene-like sequence (GLUT6). J. Biol. Chem. 265:13276–13282.PubMedGoogle Scholar
  29. Klepper, J., Diefenbach, S., Kohlschutter, A., and Voit, T. (2004). Effects of the ketogenic diet in the glucose transporter 1 deficiency syndrome. Prostaglandins Leukot. Essent. Fatty Acids 70:321–327.PubMedGoogle Scholar
  30. Kondo, F., Asanuma, M., Miyazaki, I., Kondo, Y., Tanaka, K., Makino, H., and Ogawa, N. (2001). Progressive cortical atrophy after forebrain ischemia in diabetic rats. Neurosci. Res. 39:339–346.PubMedGoogle Scholar
  31. Kriss, C. T., Lou, B.-S., Szabo, L. Z., Mitchell, S. A., Hruby, V. J., and Polt, R. (2000). Enkephalin-based drug design: Conformational analysis of O-linked glycopeptides by NMR and molecular modeling. Tetrahedron-Asymmetr. 11:9–25.Google Scholar
  32. Leino, R. L., Gerhart, D. Z., Duelli, R., Enerson, B. E., and Drewes, L. R. (2001). Diet-induced ketosis increases monocarboxylate transporter (MCTl) levels in rat brain. Neurochem. Int. 38:519–527.PubMedGoogle Scholar
  33. Leveugle, B., Ding, W., Laurence, F., Dehouck, M. P., Scanameo, A., Cecchelli, R., and Fillit, H. (1998). Heparin oligosaccharides that pass the blood-brain barrier inhibit beta-amyloid precursor protein secretion and heparin binding to beta-amyloid peptide. J. Neurochem. 70:736-744.PubMedCrossRefGoogle Scholar
  34. Ma, Q., Dudas, B., Hejna, M., Cornelli, U., Lee, J. M., Lorens, S., Mervis, R., Hanin, I., and Fareed, J. (2002). The blood-brain barrier accessibility of a heparin-derived oligosaccharides C3. Thromb. Res. 105:447–53.PubMedGoogle Scholar
  35. Maher, F. (1995). Immunolocalization of GLUT1 and GLUT3 glucose transporters in primary cultured neurons and glia. J. Neurosci. Res. 42:459–469.PubMedGoogle Scholar
  36. Maher, F., Davies-Hill, T. M., Lysko, P. G., Henneberry, R. C., and Simpson, I. A. (1991). Expression of two glucose transporters, GLUT1 and GLUT3. Mol. Cell Neurosci. 2:351–360.PubMedGoogle Scholar
  37. Maher, F., Vannucci, S. J., and Simpson, I. A. (1994). Glucose transporter proteins in brain. FASEB J. 8:1003–1011.PubMedGoogle Scholar
  38. McVie-Wylie, A. J., Lamson, D. R., and Chen, Y. T. (2001). Molecular cloning of a novel member of the GLUT family of transporters SLC2a10 (GLUT10), localized on chromosome 20q13.1: A candidate gene for NIDDM susceptibility. Genomics 72:113–117.PubMedGoogle Scholar
  39. Mitchell, S. A., Pratt, M. R., Hruby, V. J., and Polt, R. (2001). Solid-phase synthesis of O-linked glycopeptide analogues of enkephalin. J. Org. Chem. 66:2327–2342.PubMedGoogle Scholar
  40. Mooradian, A. D., Chung, H. C., and Shah, G. N. (1997). GLUT-l expression in the cerebra of patients with Alzheimer’s disease. Neurobiol. Aging 18:469–474.PubMedGoogle Scholar
  41. Mueckler, M. (1994). Facilitative glucose transporters. Eur. J. Biochem. 219:713–725.PubMedGoogle Scholar
  42. Nicchia, G. P., Frigeri, A., Liuzzi, G. M., and Svelto, M. (2003). Inhibition of aquaporin-4 expression in astrocytes by RNAi determines alteration in cell morphology, growth, and water transport and induces changes in ischemia-related genes. FASEB J. 17:1508–1510.PubMedGoogle Scholar
  43. Olson, A. L., and Pessin, J. E. (1996). Structure, function, and regulation of the mammalian facilitative glucose transporter gene family. Annu. Rev. Nutr. 16:235–256.PubMedGoogle Scholar
  44. Pardridge, W. M., and Boado, R. J. (2000). Molecular cloning and gene expression of the blood-brain barrier glucose transporter. In Pardridge, W. M. (ed.), The Blood-Brain Barrier, Raven, New York, pp. 395–440.Google Scholar
  45. Phay, J. E., Hussain, H. B., and Moley, J. F. (2000). Cloning and expression analysis of a novel member of the facilitative glucose transporter family, SLC2A9 (GLUT9). Genomics 66:217–220.PubMedGoogle Scholar
  46. Polt, R., Porreca, F., Szabo, L. Z., Bilsky, E. J., Davis, P., Abbruscato, T. J., Davis, T. P., Harvath, R., Yamamura, H. I., and Hruby, V. J. (1994). Glycopeptide enkephalin analogues produce analgesia in mice: Evidence for penetration of the blood-brain barrier. Proc. Natl. Acad. Sci. 91:7114–7118.PubMedGoogle Scholar
  47. Richard, D. E., and Thomas, P. D. (1997). Bioavailability and transport of peptides and peptide drugs into the brain. Peptides 18:1431–1439.Google Scholar
  48. Rodriguez, R. E., Rodriguez, F. D., Sacristan, M. P., Torres, J. L., Valencia, G., and Garcia Anton, J. M. (1989). New glycosylpeptide with high antinoceptive activity. Neurosci. Lett. 101:89– 94.PubMedGoogle Scholar
  49. Rogers, S., Macheda, M. L., Docherty, S. E., Carty, M. D., Henderson, M. A., Soeller, W. C., Gibbs, E. M., James, D. E., and Best, J. D. (2002). Identification of a novel glucose transporter-like protein, GLUT-12. Am. J. Physiol. Endocrinol. Metab. 282:E733–E738.PubMedGoogle Scholar
  50. Sasaki, T., Minoshima, S., Shiohama, A., Shinitani, A., Shimizu, A., Asakawa, S., Kawasaki, K., and Shimizu, N. (2001). Molecular cloning of a member of the facilitative glucose transporter gene family GLUT11(SLC2A11) and identification of transcription variants. Biochem. Biophys. Res. Commun. 289:1218–1224.PubMedGoogle Scholar
  51. Simpson, I. A., Appel, N. M., Hokari, M., Oki, J., Holman, G. D., Maher, F., Koehler-Stec, E. M., Vannucci, S. J., and Smith, Q. R. (1999). Blood-brain barrier glucose transporter: effects of hypo- and hyperglycemia revisited. J. Neurochem. 72:238–247.PubMedGoogle Scholar
  52. Simpson, I. A., Chundu, K. R., Davies-Hill, T., Honer, W. G., and Davies, P. (1994). Decreased concentrations of GLUT1 and GLUT3 glucose transporters in the brains of patients with Alzheimer’s disease. Ann. Neurol. 35:546–551.PubMedGoogle Scholar
  53. Simpson, I. A., Vannucci, S. J., Dejoseph, M. R., and Hawkins, R. A. (2001). Glucose transporter asymmetries in the bovine blood-brain barrier. J. Biol. Chem. 276:12725–12729.PubMedGoogle Scholar
  54. Tomatis, R., Marastoni, M., Balboni, G., Guerrini, R., Capasso, A., Sorrentino, L., Santagada, V., Caliendo, G., Lazarus, L. H., and Salvadori, S. (1997). Synthesis and pharmacological activity of deltorphin and dermorphin-related glycopeptides. J. Med. Chem. 40:2948–2952.PubMedGoogle Scholar
  55. Vannucci, S. J., Reinhart, R., Maher, F., Bondy, C. A., Lee, W. H., Vannucci, R. C., and Simpson, I. A. (1998). Alterations in GLUT1 and GLUT3 glucose transporter gene expression following unilateral hypoxia-ischemia in the immature rat brain. Dev. Brain Res. 107:255–264.Google Scholar
  56. Varga-Defterdarovic, L., Horvat, S., Chung, N. N., and Schiller, P. W. (1992). Glycoconjugates of opioid peptides: Synthesis and biological activity of [Leu5] enkephalin related glycoconjugates with amide type of linkage. Int. J. Pept. Protein Res. 39:12–17.PubMedCrossRefGoogle Scholar
  57. Waddell, I. D., Zomerschoe, A. G., Voice, M. W., and Burchell, A. (1992). Cloning and expression of a hepatic microsomal transport protein. Comparison with liver plasma-membrane glucose transport protein GLUT2. Biochem. J. 286:173–177.PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Department of Pharmacology, Marine Drug and Food InstituteOcean University of ChinaQingdaoChina
  2. 2.Department of Pharmacology, School of PharmacyShandong UniversityJinanChina
  3. 3.Chinese Academy of Medical Science and Peking Union Medical CollegeBeijingChina

Personalised recommendations