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Journal of Inherited Metabolic Disease

, Volume 23, Issue 3, pp 237–246 | Cite as

Glucose transporters: Structure, function and consequences of deficiency

  • G. K. Brown
Article

Abstract

There are two mechanisms for glucose transport across cell membranes. In the intestine and renal proximal tubule, glucose is transported against a concentration gradient by a secondary active transport mechanism in which glucose is cotransported with sodium ions. In all other cells, glucose transport is mediated by one or more of the members of the closely related GLUT family of glucose transporters. The pattern of expression of the GLUT transporters in different tissues is related to the different roles of glucose metabolism in different tissues. Primary defects in glucose transport all appear to be extremely rare and not all possible deficiencies have been identified. Deficiency of the secondary active sodium/glucose transporters result in glucose/galactose malabsorption or congenital renal glycosuriäGLUT1 deficiency produces a seizure disorder with low glucose concentration in cerebrospinal fluid and GLUT2 deficiency is the basis of the Fanconi–Bickel syndrome, which resembles type I glycogen storage disease.

Keywords

Glucose Glucose Transport Proximal Tubule Transport Mechanism Storage Disease 
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.

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REFERENCES

  1. Bjorbaek C, Echwald SM, Hubricht P, et al (1994) Genetic variants in promoters and codingregions of the muscle glycogen synthase and the insulin-responsive GLUT4 genes in NIDDM. Diabetes 43: 976–983.Google Scholar
  2. Burant CF, Takeda J, Brot Laroche E, Bell GI, Davidson NO (1992) Fructose transporter inhuman spermatozoa and small intestine is GLUT5. J Biol Chem 267: 14523–14526.Google Scholar
  3. Charron MJ, Kahn BB (1990) Divergent molecular mechanisms for insulin-resistant glucosetransport in muscle and adipose cells in vivo. J Biol Chem 265: 7994–8000.Google Scholar
  4. Chen C, Thorens B, Bonner Weir S, Weir GC, Leahy JL (1992) Recovery of glucose-inducedinsulin secretion in a rat model of NIDDM is not accompanied by return of the B-cellGLUT2 glucose trasporter. Diabetes 41: 1320–1327.Google Scholar
  5. Chen L, Alam T, Johnson JH, Hughes S, Newgard CB, Unger RH (1990) Regulation ofbeta-cell glucose trasporter gene expression. Proc Natl Acad Sci USA 87: 4088–4092.Google Scholar
  6. Cushman SW, Wardzala LJ (1980) Potential mechanism of insulin action on glucose transportin the isolated rat adipose cellff Apparent translocation of intracellular transportsystems to the plasma membrane. J Biol Chem 255: 4758–4762.Google Scholar
  7. De Vivo DC, Trifiletti RR, Jacobson RI, Ronen GM, Behmand RA, Harik SI (1991) Defectiveglucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia,seizures and developmental delay. N Engl J Med 325: 703–709.Google Scholar
  8. De Vivo DC, Garcia-Alvarez M, Ronem G, Trifiletti R (1995) Glucose transport protein deficiency: an emerging syndrome with therapeutic implications. Int Pediatr 10: 51–56.Google Scholar
  9. Desjeux J-F, Turk E, Wright E (1995) Congenital selective Nà D-glucose cotransport defects leading to renal glycosuria and congenital selective malabsorption of glucose and galactose. In Scriver CR, Beaudet AL, Sly WS, Valle D, edsff The Metabolic and Molecular Bases of Inherited Disease, 7th edn, volff 3. New York, McGraw-Hill, 3561–3580.Google Scholar
  10. Ebeling P, Bourey R, Koranyi L, et al (1993) Mechanism of enhanced insulin sensitivity in athletesff Increased blood Ñow, muscle glucose transport protein (GLUT-4) concentration,and glycogen synthase activity. J Clin Invest 92: 1623–1631.Google Scholar
  11. Eriksson J, Koranyi L, Bourey R, et al (1992) Insulin resistance in type 2 (non-insulin-dependent)diabetic patients and their relatives is not associated with a defect in the expression of the insulin-responsive glucose transporter (GLUT-4) gene in human skeletal muscle. Diabetologia 35: 143–147.Google Scholar
  12. Forsyth R, Fray A, Boutelle M, Fillenz M, Middleditch C, Burchell A (1996) A role forastrocytes in glucose delivery to neurons? Dev Neurosci 18: 360–370.Google Scholar
  13. Friedland RP, Jagust WJ, Huesman RHE, et al (1989) Regional cerebral glucose transport and utilisation in AlzheimerÏs disease. Neurology 39: 1427–1434.Google Scholar
  14. Garvey WT, Huecksteadt TP, Birnbaum MJ (1989) Pretranslational suppression of aninsulin-responsive glucose transporter in rats with diabetes mellitusff Science 245: 60–63.Google Scholar
  15. Garvey WT, Maianu L, Huecksteadt TP, Birnbaum MJ, Molina JM, Ciaraldi TP (1991)Pretranslational suppression of a glucose transporter protein causes insulin resistance inadipocytes from patients with non-insulin-dependent diabetes mellitus and obesity. J ClinInvest 87: 1072–1081.Google Scholar
  16. Gibbs EM, Stock JL, McCoid SC, et al (1995) Glycemic improvement in diabetic db/db miceby overexpression of the human insulin-regulatable glucose transporter (GLUT4). J ClinInvest 95: 1512–1518.Google Scholar
  17. Gould GW, Thomas HM, Jess TJ, Bell GI (1991) Expression of human glucose transportersin Xenopus oocytes: kinetic characterization and substrate specificities of the erythrocyte,liver, and brain isoforms. Biochemistry 30: 5139–5145.Google Scholar
  18. Guillam MT, Burcelin R, Thorens B (1998) Normal hepatic glucose production in theabsence of GLUT2 reveals an alternative pathway for glucose release from hepatocytes. Proc Natl Acad Sci USA 95: 12317–12321.Google Scholar
  19. James DE, Strube M, Mueckler M (1989) Molecular cloning and characterization of aninsulin-regulatable glucose transporter. Nature 338: 83–87.Google Scholar
  20. Kainulainen H, Breiner M, Schurmann A, Marttinen A, Virjo A, Joost HG (1994) In vivoglucose uptake and glucose transporter proteins GLUT1 and GLUT4 in heart and varioustypes of skeletal muscle from streptozotocin-diabetic rats. Biochim Biophys Acta 1225: 275–282.Google Scholar
  21. Katz EB, Stenbit AE, Hatton K, DePinho R, Charron MJ (1995) Cardiac and adipose tissueabnormalities but not diabetes in mice deficient in GLUT4. Nature 377: 151–155.Google Scholar
  22. Katz EB, Burcelin R, Tsao TS, Stenbit AE, Charron MJ (1996) The metabolic consequencesof altered glucose transporter expression in transgenic mice. J Mol Med 74: 639–652.Google Scholar
  23. Kayano T, Burant CF, Fukumoto H, et al (1990) Human facilitative glucose transportersff Isolation, functional characterization, and gene localization of cDNAs encoding an isoform(GLUT5) expressed in small intestine, kidney, muscle, and adipose tissue and an unusualglucose transporter pseudogene-like sequence (GLUT6). J Biol Chem 265: 13276–13282.Google Scholar
  24. Kim Y, Tamura T, Iwashita S, Tokuyama K, Suzuki M (1994) Effect of high-fat diet on geneexpression of GLUT4 and insulin receptor in soleus muscle. Biochem Biophys Res Commun 202: 519–526.Google Scholar
  25. Klepper J, Wang D, Fischbarg J, et al (1999) Defective glucose transport across brain tissuebarriers: a newly recognized neurological syndrome. Neurochem Res 24: 587–594.Google Scholar
  26. Koranyi L, Bourey R, Turk J, Mueckler M, Permutt MA (1992) Differential expression of ratpancreatic islet beta-cell glucose transporter (GLUT2), proinsulin and islet amyloid polypeptidegenes after prolonged fasting, insulin-induced hypoglycaemia and dexamethasonetreatment. Diabetologia 35: 1125–1132.Google Scholar
  27. Lesage S, Zouali H, Vionnet N, et al (1997) Genetic analyses of glucose transporter genes inFrench non-insulin-dependent diabetic families. Diabetes Metab 23: 137–142.Google Scholar
  28. MacKenzie B, Panayatova-Heiermann M, Loo DDF, Lever JE, Wright EM (1994) SAAT1 isa low affinity NA+/glucose cotransporter and not an amino acid transporter. J Biol Chem 269: 22488–22491.Google Scholar
  29. Maher F, Vannucci SJ, Simpson IA (1994) Glucose transporter proteins in brain. FASEB J 8:1003–1011.Google Scholar
  30. Mantych GJ, James DE, Chung HD, Devaskar SU (1992) Cellular localization and characterizationof Glut3 glucose transporter isoform in human brain. Endocrinology 131: 1270–1278.Google Scholar
  31. Martin MG, Lostao MP, Turk E, Lam J, Kreman M, Wright EM (1997) Compound missensemutations in the sodium/D-glucose cotransporter result in trafficking defects. Gastroenterology 112: 1206–1212.Google Scholar
  32. Miyamoto K, Hase K, Takagi T, et al (1993) Differential responses of intestinal glucose transportermRNA transcripts to levels of dietary sugars. Biochem J 295: 211–215.Google Scholar
  33. Mueckler M (1994) Facilitative glucose transporters. Eur J Biochem 219: 713–725.Google Scholar
  34. Nishimura H, Pallardo FV, Seidner GA, Vannucci S, Simpson IA, Birnbaum MJ (1993)Kinetics of GLUT1 and GLUT4 glucose transporters expressed in Xenopus oocytes. J BiolChem 268: 8514–8520.Google Scholar
  35. Olson AL, Pessin JE (1996) Structure, function, and regulation of the mammalian facilitativeglucose transporter gene family. Annu Rev Nutr 16: 235–256.Google Scholar
  36. Orci L, Unger RH, Ravazzola M, et al (1990) Reduced beta-cell glucose transporter in newonset diabetic BB rats. J Clin Invest 86: 1615–1622.Google Scholar
  37. Pedersen O, Kahn CR, Flier JS, Kahn BB (1991) High fat feeding causes insulin resistanceand a marked decrease in the expression of glucose transporters (Glut4) in fat cells of rats. Endocrinology 129: 771–777.Google Scholar
  38. Postic C, Burcelin R, Rencurel F, et al (1993) Evidence for a transient inhibitory effect ofinsulin on GLUT2 expression in the liver: studies in vivo and in vitro. Biochem J 293:119–124.Google Scholar
  39. Rossetti L, Stenbit AE, Chen W, et al (1997) Peripheral but not hepatic insulin resistance inmice with one disrupted allele of the glucose transporter type 4 (GLUT4) gene. J ClinInvest 100: 1831–1839.Google Scholar
  40. Santer R, Schneppenheim R, Suter D, Schaub J, Steinmann B (1998) Fanconi-Bickel syndrome-the original patient and his natural history, historical steps leading to theprimary defect, and a review of the literature. Eur J Pediatr 157: 783–797.Google Scholar
  41. Seidner G, Alvarez MG, Yeh JI, et al (1998) GLUT-1 deficiency syndrome caused by haploinsufficiencyof the blood-brain barrier hexose carrier. Nature Genetics 18: 188–191.Google Scholar
  42. Simpson IA, Appel NM, Hokari M, et al (1999) Blood-brain barrier glucose transporter:effects of hypo-and hyperglycemia revisited. J Neurochem 72: 238–247.Google Scholar
  43. Simpson IA, Chundu KR, Davies-Hill TM, Honer WG, Davies P (1994) Decreased concentrationsof GLUT1 and GLUT3 glucose transporters in the brains of patients with AlzheimerÏs disease. Ann Neurol 35: 546–551.Google Scholar
  44. Stenbit AE, Tsao TS, Li J, et al (1997) GLUT4 heterozygous knockout mice develop muscleinsulin resistance and diabetes. Nature Medicine 3: 1096–1101.Google Scholar
  45. Suzuki K, Kono T (1980) Evidence that insulin causes translocation of glucose transportactivity to the plasma membrane from an intracellular storage site. Proc Natl Acad SciUSA 77: 2542–2545.Google Scholar
  46. Thorens B, Wu YJ, Leahy JL, Weir GC (1992) The loss of GLUT2 expression by glucoseunresponsivebeta cells of db/db mice is reversible and is induced by the diabetic environment. J Clin Invest 90: 77–85.Google Scholar
  47. Treadway JL, Hargrove DM, Nardone NA, et al (1994) Enhanced peripheral glucose utilizationin transgenic mice expressing the human GLUT4 gene. J Biol Chem 269: 29956–29961.Google Scholar
  48. Turk E, Martin MG, Wright EM (1994) Structure of the human Nà glucose cotransportergene SGLT1. J Biol Chem 269: 15204–15209.Google Scholar
  49. Turner RJ, Moran A (1982) Heterogeneity of sodium-dependent D-glucose transport alongthe proximal tubule: evidence from vesicle studies. Am J Physiol 242: F406–414.Google Scholar
  50. Uehara Y, Nipper V, McCall AL (1997) Chronic insulin hypoglycemia induces GLUT-3protein in rat brain neurons. Am J Physiol 272: E716–719.Google Scholar
  51. Vannucci SJ (1994) Developmental expression of GLUT1 and GLUT3 glucose transportersin rat brain. J Neurochem 62: 240–246.Google Scholar
  52. Vannucci SJ, Reinhart R, Maher F, et al (1998) Alterations in GLUT1 and GLUT3 glucosetransporter gene expression following unilateral hypoxia-ischemia in the immature ratbrain. Brain Res Dev Brain Res 107: 255–264.Google Scholar
  53. Waddell ID, Zomershoe AG, Burchell A (1992) Cloning and expression of a hepatic microsomaltransport proteinff Comparison with liver plasma-membrane glucose transportprotein GLUT2. Biochem J 286: 173–177.Google Scholar
  54. Ziel FH, Venkatesan N, Davidson MB (1988) Glucose transport is rate limiting for skeletalmuscle glucose metabolism in normal and STZ-induced diabetic rats. Diabetes 37: 885–890.Google Scholar

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • G. K. Brown
    • 1
  1. 1.Genetics UnitDepartment of BiochemistryOxfordUK

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