Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jun;87(11):4261–4264. doi: 10.1073/pnas.87.11.4261

Glucose transporters are abundant in cells with "occluding" junctions at the blood-eye barriers.

S I Harik 1, R N Kalaria 1, P M Whitney 1, L Andersson 1, P Lundahl 1, S R Ledbetter 1, G Perry 1
PMCID: PMC54088  PMID: 2190218

Abstract

We studied the distribution of the "erythroid/brain" glucose transporter protein in the human and rat eye by immunocytochemistry with monoclonal and polyclonal antibodies to the C terminus of the human erythrocyte glucose transporter. We found intense immunocytochemical staining in the endothelium of microvessels of the retina, optic nerve, and iris but not in microvessels of the choroid, ciliary body, sclera, and other retro-orbital tissues. In addition, we found marked immunocytochemical staining of retinal pigment epithelium, ciliary body epithelium, and posterior epithelium of the iris. The common feature of all those endothelial and epithelial cells that stained intensely for the glucose transporter is the presence of "occluding" intercellular junctions, which constitute the anatomical bases of the blood-eye barriers. We propose that a high density of the glucose transporter is a biochemical concomitant of epithelial and endothelial cells with barrier characteristics, at least in tissues that have a high metabolic requirement for glucose.

Full text

PDF
4261

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson L., Lundahl P. C-terminal-specific monoclonal antibodies against the human red cell glucose transporter. Epitope localization with synthetic peptides. J Biol Chem. 1988 Aug 15;263(23):11414–11420. [PubMed] [Google Scholar]
  2. Asano T., Shibasaki Y., Kasuga M., Kanazawa Y., Takaku F., Akanuma Y., Oka Y. Cloning of a rabbit brain glucose transporter cDNA and alteration of glucose transporter mRNA during tissue development. Biochem Biophys Res Commun. 1988 Aug 15;154(3):1204–1211. doi: 10.1016/0006-291x(88)90268-9. [DOI] [PubMed] [Google Scholar]
  3. Baldwin S. A., Cairns M. T., Gardiner R. M., Ruggier R. A D-glucose-sensitive cytochalasin B binding component of cerebral microvessels. J Neurochem. 1985 Aug;45(2):650–652. doi: 10.1111/j.1471-4159.1985.tb04039.x. [DOI] [PubMed] [Google Scholar]
  4. Barsky S. H., Baker A., Siegal G. P., Togo S., Liotta L. A. Use of anti-basement membrane antibodies to distinguish blood vessel capillaries from lymphatic capillaries. Am J Surg Pathol. 1983 Oct;7(7):667–677. doi: 10.1097/00000478-198310000-00007. [DOI] [PubMed] [Google Scholar]
  5. Birnbaum M. J., Haspel H. C., Rosen O. M. Cloning and characterization of a cDNA encoding the rat brain glucose-transporter protein. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5784–5788. doi: 10.1073/pnas.83.16.5784. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Birnbaum M. J. Identification of a novel gene encoding an insulin-responsive glucose transporter protein. Cell. 1989 Apr 21;57(2):305–315. doi: 10.1016/0092-8674(89)90968-9. [DOI] [PubMed] [Google Scholar]
  7. Brightman M. W., Reese T. S. Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol. 1969 Mar;40(3):648–677. doi: 10.1083/jcb.40.3.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Charron M. J., Brosius F. C., 3rd, Alper S. L., Lodish H. F. A glucose transport protein expressed predominately in insulin-responsive tissues. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2535–2539. doi: 10.1073/pnas.86.8.2535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Crone C. Facilitated transfer of glucose from blood into brain tissue. J Physiol. 1965 Nov;181(1):103–113. doi: 10.1113/jphysiol.1965.sp007748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Crone C. The permeability of brain capillaries to non-electrolytes. Acta Physiol Scand. 1965 Aug;64(4):407–417. doi: 10.1111/j.1748-1716.1965.tb04198.x. [DOI] [PubMed] [Google Scholar]
  11. Dick A. P., Harik S. I. Distribution of the glucose transporter in the mammalian brain. J Neurochem. 1986 May;46(5):1406–1411. doi: 10.1111/j.1471-4159.1986.tb01755.x. [DOI] [PubMed] [Google Scholar]
  12. Dick A. P., Harik S. I., Klip A., Walker D. M. Identification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity. Proc Natl Acad Sci U S A. 1984 Nov;81(22):7233–7237. doi: 10.1073/pnas.81.22.7233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. FARQUHAR M. G., PALADE G. E. Junctional complexes in various epithelia. J Cell Biol. 1963 May;17:375–412. doi: 10.1083/jcb.17.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Flier J. S., Mueckler M., McCall A. L., Lodish H. F. Distribution of glucose transporter messenger RNA transcripts in tissues of rat and man. J Clin Invest. 1987 Feb;79(2):657–661. doi: 10.1172/JCI112864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fukumoto H., Kayano T., Buse J. B., Edwards Y., Pilch P. F., Bell G. I., Seino S. Cloning and characterization of the major insulin-responsive glucose transporter expressed in human skeletal muscle and other insulin-responsive tissues. J Biol Chem. 1989 May 15;264(14):7776–7779. [PubMed] [Google Scholar]
  16. Fukumoto H., Seino S., Imura H., Seino Y., Eddy R. L., Fukushima Y., Byers M. G., Shows T. B., Bell G. I. Sequence, tissue distribution, and chromosomal localization of mRNA encoding a human glucose transporter-like protein. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5434–5438. doi: 10.1073/pnas.85.15.5434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Haspel H. C., Rosenfeld M. G., Rosen O. M. Characterization of antisera to a synthetic carboxyl-terminal peptide of the glucose transporter protein. J Biol Chem. 1988 Jan 5;263(1):398–403. [PubMed] [Google Scholar]
  18. James D. E., Strube M., Mueckler M. Molecular cloning and characterization of an insulin-regulatable glucose transporter. Nature. 1989 Mar 2;338(6210):83–87. doi: 10.1038/338083a0. [DOI] [PubMed] [Google Scholar]
  19. Janzer R. C., Raff M. C. Astrocytes induce blood-brain barrier properties in endothelial cells. Nature. 1987 Jan 15;325(6101):253–257. doi: 10.1038/325253a0. [DOI] [PubMed] [Google Scholar]
  20. Kaestner K. H., Christy R. J., McLenithan J. C., Braiterman L. T., Cornelius P., Pekala P. H., Lane M. D. Sequence, tissue distribution, and differential expression of mRNA for a putative insulin-responsive glucose transporter in mouse 3T3-L1 adipocytes. Proc Natl Acad Sci U S A. 1989 May;86(9):3150–3154. doi: 10.1073/pnas.86.9.3150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kalaria R. N., Gravina S. A., Schmidley J. W., Perry G., Harik S. I. The glucose transporter of the human brain and blood-brain barrier. Ann Neurol. 1988 Dec;24(6):757–764. doi: 10.1002/ana.410240610. [DOI] [PubMed] [Google Scholar]
  22. Kasanicki M. A., Cairns M. T., Davies A., Gardiner R. M., Baldwin S. A. Identification and characterization of the glucose-transport protein of the bovine blood/brain barrier. Biochem J. 1987 Oct 1;247(1):101–108. doi: 10.1042/bj2470101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kayano T., Fukumoto H., Eddy R. L., Fan Y. S., Byers M. G., Shows T. B., Bell G. I. Evidence for a family of human glucose transporter-like proteins. Sequence and gene localization of a protein expressed in fetal skeletal muscle and other tissues. J Biol Chem. 1988 Oct 25;263(30):15245–15248. [PubMed] [Google Scholar]
  24. Mueckler M., Caruso C., Baldwin S. A., Panico M., Blench I., Morris H. R., Allard W. J., Lienhard G. E., Lodish H. F. Sequence and structure of a human glucose transporter. Science. 1985 Sep 6;229(4717):941–945. doi: 10.1126/science.3839598. [DOI] [PubMed] [Google Scholar]
  25. Oka Y., Asano T., Shibasaki Y., Kasuga M., Kanazawa Y., Takaku F. Studies with antipeptide antibody suggest the presence of at least two types of glucose transporter in rat brain and adipocyte. J Biol Chem. 1988 Sep 15;263(26):13432–13439. [PubMed] [Google Scholar]
  26. Raviola G., Butler J. M. Unidirectional transport mechanism of horseradish peroxidase in the vessels of the iris. Invest Ophthalmol Vis Sci. 1984 Jul;25(7):827–836. [PubMed] [Google Scholar]
  27. Raviola G. The structural basis of the blood-ocular barriers. Exp Eye Res. 1977;25 (Suppl):27–63. doi: 10.1016/s0014-4835(77)80009-2. [DOI] [PubMed] [Google Scholar]
  28. Reese T. S., Karnovsky M. J. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 1967 Jul;34(1):207–217. doi: 10.1083/jcb.34.1.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Risau W., Hallmann R., Albrecht U., Henke-Fahle S. Brain induces the expression of an early cell surface marker for blood-brain barrier-specific endothelium. EMBO J. 1986 Dec 1;5(12):3179–3183. doi: 10.1002/j.1460-2075.1986.tb04627.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Shakib M., Cunha-Vaz J. G. Studies on the permeability of the blood-retinal barrier. IV. Junctional complexes of the retinal vessels and their role in the permeability of the blood-retinal barrier. Exp Eye Res. 1966 Jul;5(3):229–234. doi: 10.1016/s0014-4835(66)80011-8. [DOI] [PubMed] [Google Scholar]
  31. Smith R. S., Rudt L. A. Ocular vascular and epithelial barriers to microperoxidase. Invest Ophthalmol. 1975 Jul;14(7):556–560. [PubMed] [Google Scholar]
  32. Smith R. S. Ultrastructural studies of the blood-aqueous barrier. I. Transport of an electron-dense tracer in the iris and ciliary body of the mouse. Am J Ophthalmol. 1971 May;71(5):1066–1077. [PubMed] [Google Scholar]
  33. Sternberger N. H., Sternberger L. A. Blood-brain barrier protein recognized by monoclonal antibody. Proc Natl Acad Sci U S A. 1987 Nov;84(22):8169–8173. doi: 10.1073/pnas.84.22.8169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Thorens B., Sarkar H. K., Kaback H. R., Lodish H. F. Cloning and functional expression in bacteria of a novel glucose transporter present in liver, intestine, kidney, and beta-pancreatic islet cells. Cell. 1988 Oct 21;55(2):281–290. doi: 10.1016/0092-8674(88)90051-7. [DOI] [PubMed] [Google Scholar]
  35. Vegge T. An electron microscopic study of the permeability of iris capillaries to horseradish peroxidase in the vervet monkey (Cercopithecus aethiops). Z Zellforsch Mikrosk Anat. 1971;121(1):74–81. doi: 10.1007/BF00330918. [DOI] [PubMed] [Google Scholar]
  36. Weiler-Güttler H., Zinke H., Möckel B., Frey A., Gassen H. G. cDNA cloning and sequence analysis of the glucose transporter from porcine blood-brain barrier. Biol Chem Hoppe Seyler. 1989 May;370(5):467–473. doi: 10.1515/bchm3.1989.370.1.467. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES