Skip to main content
Log in

Function and presumed molecular structure of Na+-D-glucose cotransport systems

  • Topical Review
  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Abstract

Functional characterization of Na+-d-glucose cotransport in intestine and kidney indicates the existence of heterogeneous Na+-d-glucose cotransport systems. Target size analysis of the transporting unit and model analysis of substrate binding have been performed and proteins have been cloned which mediate (SGLT1) and modulate (RS1) the expression of Na+-d-glucose cotransport. The experiments support the hypothesis that functional Na+-d-glucose cotransport systems in mammals are composed of two SGLT1-type subunits and may contain one or two RS1-type proteins. SGLT1 contains up to twelve membrane-spanning α-helices, whereas RS1 is a hydrophilic extracellular protein which is anchored in the brush-border membrane by a hydrophobic α-helix at the C-terminus. SGLT1 alone is able to translocate glucose together with sodium; however, RS1 increases the V max of transport expressed by SGLT1. In addition, the biphasic glucose dependence of transport, which is typical for kidney and has been often observed in intestine, was only obtained after coexpression of SGLT1 and RS1.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Alvarado, F. 1966. Transport of sugars and amino acids in the intestine: evidence for a common carrier. Science 151:1010–1013

    Google Scholar 

  2. Aronson, P.S. 1978. Energy-dependence of phlorizin binding to isolated renal microvillus membranes. Evidence concerning the mechanism of coupling between the electrochemical Na+ gradient and sugar transport. J. Membrane Biol. 42:81–98

    Google Scholar 

  3. Barfuss, D.W., Schafer, J.A. 1981. Differences in active and passive glucose transport along the proximal nephron. Am. J. Physiol. 240:F322-F332

    Google Scholar 

  4. Béliveau, R., Demeule, M., Ibnoul-Khatib, H., Bergeron, M., Beauregard, G., Potier, M. 1988. Radiation-inactivation studies on brush-border-membrane vesicles. General considerations, and application to the glucose and phosphate carriers. Biochem. J. 252:807–813

    Google Scholar 

  5. Bertran, J., Werner, A., Moore, M.L., Stange, G., Markovich, D., Biber, J., Testar, X., Zorzano, A., Palacin, M., Murer, H. 1992. Expression cloning of a cDNA from rabbit kidney cortex that induces a single transport system for cystine and dibasic and neutral amino acids. Proc. Natl. Acad. Sci. USA 89:5601–5605

    Google Scholar 

  6. Birnir, B., Lee, H.-S., Hediger, M.A., Wright, E.M. 1990. Expression and characterization of the intestinal Na+/glucose cotransporter in COS-7 cells. Biochim. Biophys. Acta 1048:100–104

    Google Scholar 

  7. Blakely, R.D., Clark, J.A., Rudnick, G., Amara, S.G. 1991. Vaccinia-T7 RNA polymerase expression system: Evaluation for the expression cloning of plasma membrane transporters. Anal. Biochem. 194:302–308

    Google Scholar 

  8. Blank, M.E., Bode, F., Baumann, K., Diedrich, D.F. 1989. Computer analysis reveals changes in renal Na+-glucose cotransporter in diabetic rats. Am. J. Physiol. 257:C385-C396

    Google Scholar 

  9. Blank, M.E., Bode, F., Huland, E., Diedrich, D.F., Baumann, K. 1985. Kinetic studies of d-glucose transport in renal brush-border membrane vesicles of streptozotocin-induced diabetic rats. Biochim. Biophys. Acta 844:314–319

    Google Scholar 

  10. Brot-Laroche, E., Dao, M.T., Alcalde, A.I., Delhomme, B., Triadou, N., Alvarado, F. 1988. Independent modulation by food supply of two distinct sodium-activated d-glucose transport systems in the guinea pig jejunal brush-border membrane. Proc. Natl. Acad. Sci. USA 85:6370–6373

    Google Scholar 

  11. Brot-Laroche, E., Serrano, M.-A., Delhomme, B., Alvarado, F. 1986. Temperature sensitivity and substrate specificity of two distinct Na+-activated d-glucose transport systems in guinea pig jejunal brush-border membrane vesicles. J. Biol. Chem. 261: 6168–6176

    Google Scholar 

  12. Burckhardt, B., Kinne, R.K.H. 1992. Cotransporters and countertransporters. In: The Kidney: Physiology and Pathophysiology. D.W. Seldin and G. Giebisch, editors, pp. 537–586. Raven, New York

    Google Scholar 

  13. Charron M.J., Brosius, F.C., III, Alper, S.L., Lodish, H.F. 1989. A glucose transport protein expressed predominately in insulinresponsive tissues. Proc. Natl. Acad. Sci. USA 86:2535–2539

    Google Scholar 

  14. Coady, M.I., Pajor, A.M., Wright, E.M. 1990. Sequence homologies among intestinal and renal Na+/glucose Cotransporters. Am. J. Physiol. 259:C605-C610

    Google Scholar 

  15. Crane, R. K. 1960. Intestinal absorption of sugars. Physiol. Rev. 40:789–825

    Google Scholar 

  16. Crane, R.K., Mandelstam, P. 1960. The active transport of sugars by various preparations of hamster intestine. Biochim. Biophys. Acta 45:460–476

    Google Scholar 

  17. Csáky, T.Z., Thale, M. 1960. Effect of ionic environment on intestinal sugar transport. J. Physiol. 151:59–65.

    Google Scholar 

  18. Debiec, H., Cross, H.S., Peterlik, M. 1991. 1,25-Dihydroxycholecalciferol-related Na+/d-glucose transport in brush-border membrane vesicles from embryonic chick jejunum. Modulation by triiodothyronine. Eur. J. Biochem. 201:709–713

    Google Scholar 

  19. Dorando, F.C., Crane, R.K. 1984. Studies of the kinetics of Na+ gradient-coupled glucose transport as found in brush-border membrane vesicles from rabbit jejunum. Biochim. Biophys. Acta 772:273–287

    Google Scholar 

  20. Elsas, L.J., Hillman, R.E., Patterson, J.H., Rosenberg, L.E. 1970. Renal and intestinal hexose transport in familial glucosegalactose malabsorption. J. Clin. Invest. 49:576–585

    Google Scholar 

  21. Ferraris, R.P., Diamond, J. 1992. Crypt-villus site of glucose transporter induction by dietary carbohydrate in mouse intestine. Am. J. Physiol. 262:G1069-G1073

    Google Scholar 

  22. Ferraris, R.P., Diamond, J.M. 1986. Use of phlorizin binding to demonstrate induction of intestinal glucose transporters. J. Membrane Biol. 94:77–82

    Google Scholar 

  23. Ferraris, R.P., Diamond, J.M. 1986. A method for measuring apical glucose transporter site density in intact intestinal mucosa by means of phlorizin binding. J. Membrane Biol. 94:65–75

    Google Scholar 

  24. Ferraris, R.P., Villenas, S.A., Hirayama, B.A., Diamond, J. 1992. Effect of diet on glucose transporter site density along the intestinal crypt-villus axis. Am. J. Physiol. 262:G1060-G1068

    Google Scholar 

  25. Freeman, H.J., Quamme, G.A. 1986. Age-related changes in sodium-dependent glucose transport in rat small intestine. Am. J. Physiol. 251:G208-G217

    Google Scholar 

  26. Freeman, T.C., Heavens, R.P., Dyer, I., Sirinathsinghji, D.J.S., Shirazi-Beechey, S.P. 1992. The expression of the Na+/glucose cotransporter in the lamb small intestine. Biochem. Soc. Trans. 20:1868

    Google Scholar 

  27. Gibbs, E.M., Hosang, M., Reber, B.F.X., Semenza, G., Diedrich, D.F. 1982. 4-azidophlorizin, a high affinity probe and photoaffinity label for the glucose transporter in brush border membranes. Biochim. Biophys. Acta 688:547–556

    Google Scholar 

  28. Guastella, I., Nelson, N., Nelson, H., Czyzyk, L., Keynan, S., Miedel, M.C., Davidson, N., Lester, H.A., Kanner, B.I. 1990. Cloning and expression of a rat brain GABA transporter. Science 249:1303–1306

    Google Scholar 

  29. Haase, W., Heitmann, K., Friese, W., Ollig, D., Koepsell, H. 1990. Characterization and histochemical localization of the rat intestinal Na+-d-glucose cotransporter by monoclonal antibodies. Eur. J. Cell Biol. 52:297–309

    Google Scholar 

  30. Haase, W., Koepsell, H. 1989. Electron microscopic immunohistochemical localization of components of Na+-cotransporters along the rat nephron. Eur. J. Cell Biol. 48:360–374

    Google Scholar 

  31. Harig, J.M., Barry, J.A., Rajendran, V.M., Soergel, K.H., Ramaswamy, K. 1989. d-glucose and l-leucine transport by human intestinal brush-border membrane vesicles. Am. J. Physiol. 256:G618-G623

    Google Scholar 

  32. Hazzard, C.E., Ahearn, G.A. 1992. Rapid stimulation of intestinal d-glucose transport in teleosts by 17α-methyltestosterone. Am. J. Physiol. 262:R412-R418

    Google Scholar 

  33. Hediger, M.A., Budarf, ML., Emanuel, B.S., Mohandas, T.K., Wright, E.M. 1989. Assignment of the human intestinal Na+/glucose cotransporter gene (SGLT1) to the q11.2-qter region of chromosome 22. Genomics 4:297–350

    Google Scholar 

  34. Hediger, M.A., Coady, M.J., Ikeda, T.S., Wright, E.M. 1987. Expression cloning and cDNA sequencing of the Na+/glucose Cotransporter. Nature 330:379–381

    Google Scholar 

  35. Hediger, M.A., Ikeda, T., Coady, M., Gundersen, C.B., Wright, E.M. 1987. Expression of size-selected mRNA encoding the intestinal Na/glucose cotransporter in Xenopus laevis oocytes. Proc. Natl. Acad. Sci. USA 84:2634–2637

    Google Scholar 

  36. Hediger, M.A., Mendlein, J., Lee, H.-S., Wright, E.M. 1991. Biosynthesis of the cloned intestinal Na+/glucose cotransporter. Biochim. Biophys. Acta 1064:360–364

    Google Scholar 

  37. Hediger, M.A., Turk, E., Wright, E.M. 1989. Homology of the human intestinal Na+/glucose and Escherichia coli Na+/proline cotransporters. Proc. Natl. Acad. Sci. USA 86:5748–5752

    Google Scholar 

  38. Honold, K., Ludeke, B., Hengartner, H., Semenza, G. 1988. Stimulation of intestinal Na+/d-glucose cotransport by monoclonal antibodies. J. Membrane Biol. 105:165–175

    Google Scholar 

  39. Hopfer, U., Nelson, K., Perrotto, J., Isselbacher, K.J. 1973. Glucose transport in isolated brush border membrane from rat small intestine. J. Biol. Chem. 248:25–32

    Google Scholar 

  40. Hopfer, U., Sigrist-Nelson, K., Groseclose, R. 1976. Jejunal and ileal d-glucose transport in isolated brush border membranes. Biochim. Biophys. Acta 426:349–353

    Google Scholar 

  41. Hosang, M, Gibbs, E.M., Diedrich, D.F., Semenza, G. 1981. Photoaffinity labeling and identification of (a component of) the small-intestinal Na+, d-glucose transporter using 4-azidophlorizin. FEBS Lett. 130:244–248

    Google Scholar 

  42. Ikeda, T.S., Hwang, E.-S., Coady, M.J., Hirayama, B.A., Hediger, M.A., Wright, E.M. 1989. Characterization of a Na+/glucose cotransporter cloned from rabbit small intestine. J. Membrane Biol. 110:87–95

    Google Scholar 

  43. Jackowski, S., Alix, J.-H. 1990. Cloning, sequence and expression of the pantothenate permease (panF) gene of Escherichia coli. J. Bacteriol. 172:3842–3848

    Google Scholar 

  44. Kanai, Y., Hediger, M.A. 1992. Primary structure and functional characterization of a high-affinity glutamate transporter. Nature 360:467–471

    Google Scholar 

  45. Kaunitz, J.D., Gunther, R., Wright, E.M. 1982. Involvement of multiple sodium ions in intestinal d-glucose transport. Proc. Natl. Acad. Sci. USA 79:2315–2318

    Google Scholar 

  46. Kaunitz, J.D., Wright, E.M. 1984. Kinetics of sodium d-glucose cotransport in bovine intestinal brush border vesicles. J. Membrane Biol. 79:41–51

    Google Scholar 

  47. Kimmich, G.A. 1990. Membrane potentials and the mechanism of intestinal Na+-dependent sugar transport. J. Membrane Biol. 114:1–27

    Google Scholar 

  48. Kimmich, G.A., Randies, J. 1973. Interaction between Na+-dependent transport systems for sugars and amino acids. Evidence against a role for the sodium gradient. J. Membrane Biol. 12:47–68

    Google Scholar 

  49. Kimmich, G.A., Randles, J. 1980. Evidence for an intestinal Na+: sugar transport coupling stoichiometry of 2.0. Biochim. Biophys. Acta 596:439–444

    Google Scholar 

  50. Kinne, R., Murer, H., Kinne-Saffran, E., Thees, M., Sachs, G. 1975. Sugar transport by renal plasma membrane vesicles. Characterization of the systems in the brush-border microvilli and basal-lateral plasma membranes. J. Membrane Biol. 21:375–395

    Google Scholar 

  51. Koepsell, H., Fritzsch, G., Korn, K., Madrala, A. 1990. Two substrate sites in the renal Na+-d-glucose cotransporter studied by model analysis of phlorizin binding and d-glucose transport measurements. J. Membrane Biol. 114:113–132

    Google Scholar 

  52. Koepsell, H., Korn, K., Raszeja-Specht, A., Bernotat-Danielowski, S., Ollig, D. 1988. Monoclonal antibodies against the renal Na+-d-glucose cotransporter. Identification of antigenic polypeptides and demonstration of functional coupling of different Na+-cotransport systems. J. Biol. Chem. 263:18419–18429

    Google Scholar 

  53. Koepsell, H., Madrala, A. 1987. Interaction of phlorizin with the Na+-d-glucose cotransporter from intestine and kidney. Top. Mol. Pharmacol. 4:169–202

    Google Scholar 

  54. Koepsell, H., Seibicke, S. 1990. Reconstitution and fractionation of renal brush border transport proteins. Methods Enzymol. 191:583–605

    Google Scholar 

  55. Kong, C.-T., Yet, S.-F., Lever, J.E. 1993. Cloning and expression of a mammalian Na+/amino acid cotransporter with sequence similarity to Na+/glucose cotransporters. J. Biol. Chem. 268:1509–1512

    Google Scholar 

  56. Kwon, H.M., Yamauchi, A., Uchida, S., Preston, A.S., Garcia-Perez, A., Burg, M.B., Handler, J.S. 1992. Cloning of the cDNA for a Na+ Imyo-inositol cotransporter, a hypertonicity stress protein. J. Biol. Chem. 267:6297–6301

    Google Scholar 

  57. Lescale-Matys, L., Dyer, J., Scott, D., Freeman, T.C., Wright, E.M., Shirazi-Beechey, S.P. 1993. Regulation of the ovine intestinal Na+/glucose co-transporter (SGLT1) is dissociated from mRNA abundance. Biochem. J. 291:435–440

    Google Scholar 

  58. Lin, J.-T., Szwarc, K., Kinne, R., Jung, C.Y. 1984. Structural state of the Na+/d-glucose cotransporter in calf kidney brushborder membranes. Target size analysis of Na+-dependent phlorizin binding and Na+-dependent d-glucose transport. Biochim. Biophys. Acta 777:208–210

    Google Scholar 

  59. Lindquist, B., Meeuwisse, G., Melin, K. 1962. Glucose-galactose malabsorption. Lancet 2:666

    Google Scholar 

  60. Malo, C. 1988. Kinetic evidence for heterogeneity in Na+-d-glucose cotransport systems in the normal human fetal small intestine. Biochim. Biophys. Acta 938:181–188

    Google Scholar 

  61. Malo, C. 1990. Separation of two distinct Na+/d-glucose Cotransport systems in the human fetal jejunum by means of their differential specificity for 3-O-methylglucose. Biochim. Biophys. Acta 1022:8–16

    Google Scholar 

  62. Malo, C., Berteloot, A. 1991. Analysis of kinetic data in transport studies: New insights from kinetic studies of Na+-d-glucose cotransport in human intestinal brush-border membrane vesicles using a fast sampling, rapid filtration apparatus. J. Membrane Biol. 122:127–141

    Google Scholar 

  63. McDonough, A.A., Geering, K., Farley, R.A. 1990. The sodium pump needs its β subunit. FASEB J. 4:1598–1605

    Google Scholar 

  64. Meeuwisse, G.W., Dahlqvist, A. 1968. Glucose-galactose malabsorption. A study with biopsy of the small intestinal mucosa. Acta Paediat. Scand. 57:273–280

    Google Scholar 

  65. Miyamoto, K.-I., Hase, K., Taketani, Y., Minami, H., Oka, T., Nakabou, Y., Hagihira, H. 1991. Diabetes and glucose transporter gene expression in rat small intestine. Biochem. Biophys. Res. Commun. 181:1110–1117

    Google Scholar 

  66. Moran, A., Turner, R.J., Handler, J.S. 1983. Regulation of sodium-coupled glucose transport by glucose in a cultured epithelium. J. Biol. Chem. 258:15087–15090

    Google Scholar 

  67. Moran, A., Turner, R.J., Handler, J.S. 1984. Hexose regulation of sodium-hexose transport in LLC-PK1 epithelia: The nature of the signal. J. Membrane Biol. 82:59–65

    Google Scholar 

  68. Morrison, A.I., Panayotova-Heiermann, M., Feigl, G., Schölermann, B., Kinne, R.K.H. 1991. Sequence comparison of the sodium-d-glucose cotransport systems in rabbit renal and intestinal epithelia. Biochim. Biophys. Acta 1089:121–123

    Google Scholar 

  69. Mueckler, M., Lodish, H.F. 1986. The human glucose transporter can insert posttranslationally into microsomes. Cell 44:629–637

    Google Scholar 

  70. Murer, H., Hopfer, U. 1974. Demonstration of electrogenic Na+-dependent d-glucose transport in intestinal brush border membranes. Proc. Natl. Acad. Sci. USA 71:484–488

    Google Scholar 

  71. Murer, H., Sigrist-Nelson, K., Hopfer, U. 1975. On the mechanism of sugar and amino acid interaction in intestinal transport. J. Biol. Chem. 250:7392–7396

    Google Scholar 

  72. Nakao, T., Yamato, I., Anraku, Y. 1987. Nucleotide sequence of putP, the proline carrier gene of Escherichia coli K12. Mol. Gen. Genet. 208:70–75

    Google Scholar 

  73. Neeb, M., Fasold, H., Koepsell, H. 1985. Identification of the d-glucose binding polypeptide of the renal Na+-d-glucose cotransporter with a covalently binding d-glucose analog. FEBS Lett. 182:139–144

    Google Scholar 

  74. Neeb, M., Kunz, U., Koepsell, H. 1987. Identification of d-glucose-binding polypeptides which are components of the renal Na+-d-glucose cotransporter. J. Biol Chem. 262:10718–10727

    Google Scholar 

  75. Noguchi, S., Maeda, M., Futai, M., Kawamura, M. 1992. Assembly of a hybrid from the α subunit of Na+/K+-ATPase and the β subunit of H+/K+-ATPase. Biochem. Biophys. Res. Commun. 182:659–666

    Google Scholar 

  76. Ohta, T., Isselbacher, K.J., Rhoads, D.B. 1990. Regulation of glucose transporters in LLC-PK1 cells: Effects of d-glucose and monosaccharides. Mol. Cell. Biol. 10:6491–6499

    Google Scholar 

  77. Pajor, A.M., Wright, E.M. 1992. Cloning and functional expression of a mammalian Na+/nucleoside cotransporter. J. Biol. Chem. 267:3557–3560

    Google Scholar 

  78. Peerce, B.E., Wright, E.M. 1984. Sodium-induced conformational changes in the glucose transporter of intestinal brush borders. J. Biol. Chem. 259:14105–14112

    Google Scholar 

  79. Peerce, B.E., Wright E.M. 1984. Conformational changes in the intestinal brush border sodium-glucose cotransporter labeled with fluorescein isothiocyanate. Proc. Natl. Acad. Sci. USA 81:2223–2226

    Google Scholar 

  80. Pines, G., Danbolt, N.C., Bjørås, M., Zhang, Y., Bendahan, A., Eide, L., Koepsell, H., Storm-Mathisen, J., Seeberg, E., Kanner, B.I. 1992. Cloning and expression of a rat brain l-glutamate transporter. Nature 360:464–467

    Google Scholar 

  81. Quamme, G.A., Freeman, H.J. 1987. Evidence for a high-affinity sodium-dependent d-glucose transport system in the kidney. Am. J. Physiol. 253:F151-F157

    Google Scholar 

  82. Restrepo, D., Kimmich, G.A. 1986. Phlorizin binding to isolated enterocytes: Membrane potential and sodium dependence. J. Membrane Biol. 89:269–280

    Google Scholar 

  83. Riklis, E., Quastel, J.H. 1958. Effects of cations on sugar absorption by isolated surviving guinea pig intestine. Can. J. Biochem. Physiol. 36:347–362

    Google Scholar 

  84. Schloss, P., Mayser, W., Betz, H. 1992. Neurotransmitter transporters, a novel family of integral plasma membrane proteins. FEBS Lett. 307:76–80

    Google Scholar 

  85. Schmidt, U.M., Eddy, B., Fraser, C.M., Venter, J.C., Semenza, G. 1983. Isolation of (a subunit of) the Na+/d-glucose cotransporter(s) of rabbit intestinal brush border membranes using monoclonal antibodies. FEBS Lett. 161:279–283

    Google Scholar 

  86. Scriver, C.R., Chesney, R.W., McInnes, R.R. 1976. Genetic aspects of renal tubular transport: Diversity and topology of carriers. Kidney Int. 9:149–171

    Google Scholar 

  87. Semenza, G., Kessler, M., Hosang, M., Weber, J., Schmidt, U. 1984. Biochemistry of the Na+, d-glucose cotransporter of the small-intestinal brush-border memberane. Biochim. Biophys. Acta 779:343–379

    Google Scholar 

  88. Shirazi-Beechey, S.P., Hirayama, B.A., Wang, Y., Scott, D., Smith, M.W., Wright, E.M. 1991. Ontogenetic development of lamb intestinal sodium-glucose co-transporter is regulated by diet. J. Physiol. 437:699–708

    Google Scholar 

  89. Silverman, M. 1976. Glucose transport in the kidney. Biochim. Biophys. Acta 457:303–351

    Google Scholar 

  90. Silverman, M. 1980. Participation of the ring oxygen in sugar interaction with transporters at renal tubular surfaces. Biochim. Biophys. Acta 600:502–512

    Google Scholar 

  91. Silverman, M. 1991. Structure and function of hexose transporters. Annu. Rev. Biochem. 60:757–794

    Google Scholar 

  92. Silverman, M., Aganon, M.A., Chinard, F.P. 1970. Specificity of monosaccharide transport in dog kidney. Am. J. Physiol. 218(3):743–750

    Google Scholar 

  93. Silverman, M., Turner, R.J. 1992. Glucose transport in the renal proximal tubule. In: Handbook of Physiology II. Section 8: Renal Physiology. E.E. Windhager, editor, pp. 2017–2036. Oxford University, New York

    Google Scholar 

  94. Smith, D.C., Hirayama, B.A., Wright, E.M. 1992. Baculovirusmediated expression of the Na+/glucose cotransporter in Sf9 cells. Biochim. Biophys. Acta 1104:151–159

    Google Scholar 

  95. Smith, M.W., Turvey, A., Freeman, T.C. 1992. Appearance of phloridzin-sensitive glucose transport is not controlled at mRNA level in rabbit jejunal enterocytes. Exp. Physiol. 77:525–528

    Google Scholar 

  96. Spangenberg, J., Veyhl, M., Poppe, R., Koepsell, H. 1993. Characterization of the regulatory subunit of the Na+-d-glucose cotransporter. Biol. Chem. Hoppe-Seyler 374:157

    Google Scholar 

  97. Steffgen, J., Koepsell, H., Schwarz, W. 1991. Endogeneous l-glutamate transport in oocytes of Xenopus laevis. Biochim. Biophys. Acta 1066:14–20

    Google Scholar 

  98. Stevens, B.R., Fernandez, A., Hirayama, B., Wright, E.M. 1990. Intestinal brush border membrane Na+/glucose cotransporter functions in situ as a homotetramer. Proc. Natl. Acad. Sci. USA 87:1456–1460

    Google Scholar 

  99. Stewart, C.P., Turnberg, L.A. 1987. Glucose depolarizes villous but not crypt cell apical membrane potential difference: a micropuncture study of crypt-villus heterogeneity in the rat. Biochim. Biophys. Acta 902:293–300

    Google Scholar 

  100. Storck, T., Schulte, S., Hofman, K., Stoffel, W. 1992. Structure, expression, and functional analysis of a Na+-dependent glutamate/aspartate transporter from rat brain. Proc. Natl. Acad. Sci. USA 89:10955–10959

    Google Scholar 

  101. Takahashi, M., Malathi, P., Preiser, H., Jung, C.Y. 1985. Radiation inactivation studies on the rabbit kidney sodium-dependent glucose transporter. J. Biol. Chem. 260:10551–10556

    Google Scholar 

  102. Takata, K., Kasahara, T., Kasahara, M., Ezaki, O., Hirano, H. 1992. Immunohistochemical localization of Na+-dependent glucose transporter in rat jejunum. Cell Tissue Res. 267:3–9

    Google Scholar 

  103. Toggenburger, G., Kessler, M., Rothstein, A., Semenza, G., Tannenbaum, C. 1978. Similarity in effects of Na+ gradients and membrane potentials on d-glucose transport by, and phlorizin binding to, vesicles derived from brush borders of rabbit intestinal mucosal cells. J. Membrane Biol. 40:269–290

    Google Scholar 

  104. Turk, E., Zabel, B., Mundlos, S., Dyer, J., Wright, E.M. 1991. Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. Nature 350:354–356

    Google Scholar 

  105. Turner, R.J., Kempner, E.S. 1982. Radiation inactivation studies of the renal brush-border membrane phlorizin-binding protein. J. Biol. Chem. 257:10794–10797

    Google Scholar 

  106. Turner, R.J., Moran, A. 1982. Heterogeneity of sodium-dependent d-glucose transport sites along the proximal tubule: evidence from vesicle studies. Am. J. Physiol. 242:F406-F414

    Google Scholar 

  107. Turner, R.J., Moran, A. 1982. Further studies of proximal tubular brush border membrane d-glucose transport heterogeneity. J. Membrane Biol. 70:37–45

    Google Scholar 

  108. Turner, R.J., Moran, A. 1982. Stoichiometric studies of the renal outer cortical brush border membrane d-glucose transporter. J. Membrane Biol. 67:73–80

    Google Scholar 

  109. Turner, R.J. 1983. Quantitative studies of cotransport systems: Models and vesicles. J. Membrane Biol. 76:1–15

    Google Scholar 

  110. Ullrich, K.J., Rumrich, G., Klöss, S. 1974. Specificity and sodium dependence of the active sugar transport in the proximal convolution of the rat kidney. Pfluegers Arch. 351:35–48

    Google Scholar 

  111. Veyhl, M., Püschel, B., Spangenberg, J., Dekel, C., Koepsell, H. 1992. Cloning of the β-subunit of the Na+-d-glucose symporter. FASEB J. 6:A1459

    Google Scholar 

  112. Veyhl, M, Spangenberg, J., Puschel, B., Poppe, R., Dekel, C., Fritzsch, G., Haase, W., Koepsell, H. 1993. Cloning of a membrane-associated protein which modifies activity and properties of the Na+-d-glucose cotransporter. J. Biol. Chem. 268: 25041–25053

    Google Scholar 

  113. Weber, W.-M., Püschel, B., Steffgen, J., Koepsell, H., Schwarz, W. 1991. Comparison of a Na+-d-glucose cotransporter from rat intestine expressed in oocytes of Xenopus laevis with the endogenous cotransporter. Biochim. Biophys. Acta 1063:73–80

    Google Scholar 

  114. Weber, W.-M., Schwarz, W. Passow, H. 1989. Endogenous d-glucose transport in oocytes of Xenopus laevis. J. Membrane Biol. 111:93–102

    Google Scholar 

  115. Wells, R.G., Pajor, A.M., Kanai, Y., Turk, E., Wright, E.M., Hediger, M.A. 1992. Cloning of a human kidney cDNA with similarity to the sodium-glucose cotransporter. Am. J. Physiol. 263:F459-F465

    Google Scholar 

  116. Werner, A., Moore, M.L., Mantei, N., Biber, J., Semenza, G., Murer, H. 1991. Cloning and expression of cDNA for a Na/Pi cotransport system of kidney cortex. Proc. Natl. Acad. Sci. USA 88:9608–9612

    Google Scholar 

  117. Wu, J.-S.R., Lever, J.E. 1987. Monoclonal antibodies that bind the renal Na+/glucose symport system. 1. Identification. Biochemistry 26:5783–5790

    Google Scholar 

  118. Yan, N., Mosckovitz, R., Udenfriend, S., Tate, S.S. 1992. Distribution of mRNA of a Na+-independent neutral amino acid transporter cloned from rat kidney and its expression in mammalian tissues and Xenopus laevis oocytes. Proc. Natl. Acad. Sci USA 89:9982–9985

    Google Scholar 

  119. Ziegler, K., Frimmer, M., Fritzsch, G., Koepsell, H. 1990. Cyclosporin binding to a protein component of the renal Na+-d-glucose cotransporter. J. Biol. Chem. 265:3270–3277

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koepsell, H., Spangenberg, J. Function and presumed molecular structure of Na+-D-glucose cotransport systems. J. Membarin Biol. 138, 1–11 (1994). https://doi.org/10.1007/BF00211064

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00211064

Key words

Navigation