Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 May;89(5):1367–1374. doi: 10.1172/JCI115724

Facilitative glucose transporters: regulatory mechanisms and dysregulation in diabetes.

B B Kahn 1
PMCID: PMC443004  PMID: 1569179

Full text

PDF
1367

Images in this article

Selected References

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

  1. Balch W. E. Small GTP-binding proteins in vesicular transport. Trends Biochem Sci. 1990 Dec;15(12):473–477. doi: 10.1016/0968-0004(90)90301-q. [DOI] [PubMed] [Google Scholar]
  2. Baldini G., Hohman R., Charron M. J., Lodish H. F. Insulin and nonhydrolyzable GTP analogs induce translocation of GLUT 4 to the plasma membrane in alpha-toxin-permeabilized rat adipose cells. J Biol Chem. 1991 Mar 5;266(7):4037–4040. [PubMed] [Google Scholar]
  3. Bell G. I., Kayano T., Buse J. B., Burant C. F., Takeda J., Lin D., Fukumoto H., Seino S. Molecular biology of mammalian glucose transporters. Diabetes Care. 1990 Mar;13(3):198–208. doi: 10.2337/diacare.13.3.198. [DOI] [PubMed] [Google Scholar]
  4. Berger J., Biswas C., Vicario P. P., Strout H. V., Saperstein R., Pilch P. F. Decreased expression of the insulin-responsive glucose transporter in diabetes and fasting. Nature. 1989 Jul 6;340(6228):70–72. doi: 10.1038/340070a0. [DOI] [PubMed] [Google Scholar]
  5. Biber J. W., Lienhard G. E. Isolation of vesicles containing insulin-responsive, intracellular glucose transporters from 3T3-L1 adipocytes. J Biol Chem. 1986 Dec 5;261(34):16180–16184. [PubMed] [Google Scholar]
  6. Calderhead D. M., Kitagawa K., Lienhard G. E., Gould G. W. Translocation of the brain-type glucose transporter largely accounts for insulin stimulation of glucose transport in BC3H-1 myocytes. Biochem J. 1990 Aug 1;269(3):597–601. doi: 10.1042/bj2690597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Charron M. J., Kahn B. B. Divergent molecular mechanisms for insulin-resistant glucose transport in muscle and adipose cells in vivo. J Biol Chem. 1990 May 15;265(14):7994–8000. [PubMed] [Google Scholar]
  8. Chen L., Alam T., Johnson J. H., Hughes S., Newgard C. B., Unger R. H. Regulation of beta-cell glucose transporter gene expression. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4088–4092. doi: 10.1073/pnas.87.11.4088. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chiasson J. L., Germain L., Srivastava A. K., Dupuis P. Hormonal regulation of glucose transport in contracting skeletal muscle from normal and diabetic rats. Metabolism. 1984 Jul;33(7):617–621. doi: 10.1016/0026-0495(84)90059-3. [DOI] [PubMed] [Google Scholar]
  10. Choi W. H., O'Rahilly S., Buse J. B., Rees A., Morgan R., Flier J. S., Moller D. E. Molecular scanning of insulin-responsive glucose transporter (GLUT4) gene in NIDDM subjects. Diabetes. 1991 Dec;40(12):1712–1718. doi: 10.2337/diab.40.12.1712. [DOI] [PubMed] [Google Scholar]
  11. Ciaraldi T. P. Neuraminidase treatment of isolated rat adipocytes and differential regulation of basal and insulin-stimulated glucose transport. Diabetes. 1989 Aug;38(8):951–958. doi: 10.2337/diab.38.8.951. [DOI] [PubMed] [Google Scholar]
  12. Clandinin M. T., Cheema S., Field C. J., Garg M. L., Venkatraman J., Clandinin T. R. Dietary fat: exogenous determination of membrane structure and cell function. FASEB J. 1991 Oct;5(13):2761–2769. doi: 10.1096/fasebj.5.13.1916101. [DOI] [PubMed] [Google Scholar]
  13. Clark A. E., Holman G. D., Kozka I. J. Determination of the rates of appearance and loss of glucose transporters at the cell surface of rat adipose cells. Biochem J. 1991 Aug 15;278(Pt 1):235–241. doi: 10.1042/bj2780235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. De Vivo D. C., Trifiletti R. R., Jacobson R. I., Ronen G. M., Behmand R. A., Harik S. I. Defective glucose transport across the blood-brain barrier as a cause of persistent hypoglycorrhachia, seizures, and developmental delay. N Engl J Med. 1991 Sep 5;325(10):703–709. doi: 10.1056/NEJM199109053251006. [DOI] [PubMed] [Google Scholar]
  15. DeFronzo R. A., Jacot E., Jequier E., Maeder E., Wahren J., Felber J. P. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes. 1981 Dec;30(12):1000–1007. doi: 10.2337/diab.30.12.1000. [DOI] [PubMed] [Google Scholar]
  16. Dohm G. L., Elton C. W., Friedman J. E., Pilch P. F., Pories W. J., Atkinson S. M., Jr, Caro J. F. Decreased expression of glucose transporter in muscle from insulin-resistant patients. Am J Physiol. 1991 Mar;260(3 Pt 1):E459–E463. doi: 10.1152/ajpendo.1991.260.3.E459. [DOI] [PubMed] [Google Scholar]
  17. Friedman J. E., Sherman W. M., Reed M. J., Elton C. W., Dohm G. L. Exercise training increases glucose transporter protein GLUT-4 in skeletal muscle of obese Zucker (fa/fa) rats. FEBS Lett. 1990 Jul 30;268(1):13–16. doi: 10.1016/0014-5793(90)80960-q. [DOI] [PubMed] [Google Scholar]
  18. Froehner S. C., Davies A., Baldwin S. A., Lienhard G. E. The blood-nerve barrier is rich in glucose transporter. J Neurocytol. 1988 Apr;17(2):173–178. doi: 10.1007/BF01674204. [DOI] [PubMed] [Google Scholar]
  19. Garvey W. T., Huecksteadt T. P., Birnbaum M. J. Pretranslational suppression of an insulin-responsive glucose transporter in rats with diabetes mellitus. Science. 1989 Jul 7;245(4913):60–63. doi: 10.1126/science.2662408. [DOI] [PubMed] [Google Scholar]
  20. Garvey W. T., Maianu L., Huecksteadt T. P., Birnbaum M. J., Molina J. M., Ciaraldi T. P. Pretranslational suppression of a glucose transporter protein causes insulin resistance in adipocytes from patients with non-insulin-dependent diabetes mellitus and obesity. J Clin Invest. 1991 Mar;87(3):1072–1081. doi: 10.1172/JCI115068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Goodman M. N., Berger M., Ruderman N. B. Glucose metabolism in rat skeletal muscle at rest. Effect of starvation, diabetes, ketone bodies and free fatty acids. Diabetes. 1974 Nov;23(11):881–888. doi: 10.2337/diab.23.11.881. [DOI] [PubMed] [Google Scholar]
  22. Hainault I., Guerre-Millo M., Guichard C., Lavau M. Differential regulation of adipose tissue glucose transporters in genetic obesity (fatty rat). Selective increase in the adipose cell/muscle glucose transporter (GLUT 4) expression. J Clin Invest. 1991 Mar;87(3):1127–1131. doi: 10.1172/JCI115077. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Handberg A., Vaag A., Damsbo P., Beck-Nielsen H., Vinten J. Expression of insulin regulatable glucose transporters in skeletal muscle from type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1990 Oct;33(10):625–627. doi: 10.1007/BF00400207. [DOI] [PubMed] [Google Scholar]
  24. Harrison S. A., Buxton J. M., Czech M. P. Suppressed intrinsic catalytic activity of GLUT1 glucose transporters in insulin-sensitive 3T3-L1 adipocytes. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7839–7843. doi: 10.1073/pnas.88.17.7839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Helmrich S. P., Ragland D. R., Leung R. W., Paffenbarger R. S., Jr Physical activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med. 1991 Jul 18;325(3):147–152. doi: 10.1056/NEJM199107183250302. [DOI] [PubMed] [Google Scholar]
  26. Henriksen E. J., Bourey R. E., Rodnick K. J., Koranyi L., Permutt M. A., Holloszy J. O. Glucose transporter protein content and glucose transport capacity in rat skeletal muscles. Am J Physiol. 1990 Oct;259(4 Pt 1):E593–E598. doi: 10.1152/ajpendo.1990.259.4.E593. [DOI] [PubMed] [Google Scholar]
  27. Hirshman M. F., Wardzala L. J., Goodyear L. J., Fuller S. P., Horton E. D., Horton E. S. Exercise training increases the number of glucose transporters in rat adipose cells. Am J Physiol. 1989 Oct;257(4 Pt 1):E520–E530. doi: 10.1152/ajpendo.1989.257.4.E520. [DOI] [PubMed] [Google Scholar]
  28. Houmard J. A., Egan P. C., Neufer P. D., Friedman J. E., Wheeler W. S., Israel R. G., Dohm G. L. Elevated skeletal muscle glucose transporter levels in exercise-trained middle-aged men. Am J Physiol. 1991 Oct;261(4 Pt 1):E437–E443. doi: 10.1152/ajpendo.1991.261.4.E437. [DOI] [PubMed] [Google Scholar]
  29. James D. E., Hiken J., Lawrence J. C., Jr Isoproterenol stimulates phosphorylation of the insulin-regulatable glucose transporter in rat adipocytes. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8368–8372. doi: 10.1073/pnas.86.21.8368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Johnson J. H., Newgard C. B., Milburn J. L., Lodish H. F., Thorens B. The high Km glucose transporter of islets of Langerhans is functionally similar to the low affinity transporter of liver and has an identical primary sequence. J Biol Chem. 1990 Apr 25;265(12):6548–6551. [PubMed] [Google Scholar]
  32. Johnson J. H., Ogawa A., Chen L., Orci L., Newgard C. B., Alam T., Unger R. H. Underexpression of beta cell high Km glucose transporters in noninsulin-dependent diabetes. Science. 1990 Oct 26;250(4980):546–549. doi: 10.1126/science.2237405. [DOI] [PubMed] [Google Scholar]
  33. Kahn B. B., Charron M. J., Lodish H. F., Cushman S. W., Flier J. S. Differential regulation of two glucose transporters in adipose cells from diabetic and insulin-treated diabetic rats. J Clin Invest. 1989 Aug;84(2):404–411. doi: 10.1172/JCI114180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Kahn B. B., Cushman S. W. Subcellular translocation of glucose transporters: role in insulin action and its perturbation in altered metabolic states. Diabetes Metab Rev. 1985;1(3):203–227. doi: 10.1002/dmr.5610010301. [DOI] [PubMed] [Google Scholar]
  35. Kahn B. B., Flier J. S. Regulation of glucose-transporter gene expression in vitro and in vivo. Diabetes Care. 1990 Jun;13(6):548–564. doi: 10.2337/diacare.13.6.548. [DOI] [PubMed] [Google Scholar]
  36. Kahn B. B., Horton E. S., Cushman S. W. Mechanism for enhanced glucose transport response to insulin in adipose cells from chronically hyperinsulinemic rats. Increased translocation of glucose transporters from an enlarged intracellular pool. J Clin Invest. 1987 Mar;79(3):853–858. doi: 10.1172/JCI112894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kahn B. B., Rosen A. S., Bak J. F., Andersen P. H., Damsbo P., Lund S., Pedersen O. Expression of GLUT1 and GLUT4 glucose transporters in skeletal muscle of humans with insulin-dependent diabetes mellitus: regulatory effects of metabolic factors. J Clin Endocrinol Metab. 1992 May;74(5):1101–1109. doi: 10.1210/jcem.74.5.1569156. [DOI] [PubMed] [Google Scholar]
  38. Kahn B. B., Rossetti L., Lodish H. F., Charron M. J. Decreased in vivo glucose uptake but normal expression of GLUT1 and GLUT4 in skeletal muscle of diabetic rats. J Clin Invest. 1991 Jun;87(6):2197–2206. doi: 10.1172/JCI115254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Kahn B. B., Shulman G. I., DeFronzo R. A., Cushman S. W., Rossetti L. Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression. J Clin Invest. 1991 Feb;87(2):561–570. doi: 10.1172/JCI115031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Kahn B. B., Simpson I. A., Cushman S. W. Divergent mechanisms for the insulin resistant and hyperresponsive glucose transport in adipose cells from fasted and refed rats. Alterations in both glucose transporter number and intrinsic activity. J Clin Invest. 1988 Aug;82(2):691–699. doi: 10.1172/JCI113649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Karnieli E., Zarnowski M. J., Hissin P. J., Simpson I. A., Salans L. B., Cushman S. W. Insulin-stimulated translocation of glucose transport systems in the isolated rat adipose cell. Time course, reversal, insulin concentration dependency, and relationship to glucose transport activity. J Biol Chem. 1981 May 25;256(10):4772–4777. [PubMed] [Google Scholar]
  42. Keller K., Strube M., Mueckler M. Functional expression of the human HepG2 and rat adipocyte glucose transporters in Xenopus oocytes. Comparison of kinetic parameters. J Biol Chem. 1989 Nov 15;264(32):18884–18889. [PubMed] [Google Scholar]
  43. Klip A., Marette A. Acute and chronic signals controlling glucose transport in skeletal muscle. J Cell Biochem. 1992 Jan;48(1):51–60. doi: 10.1002/jcb.240480109. [DOI] [PubMed] [Google Scholar]
  44. Koranyi L. I., Bourey R. E., Vuorinen-Markkola H., Koivisto V. A., Mueckler M., Permutt M. A., Yki-Järvinen H. Level of skeletal muscle glucose transporter protein correlates with insulin-stimulated whole body glucose disposal in man. Diabetologia. 1991 Oct;34(10):763–765. doi: 10.1007/BF00401526. [DOI] [PubMed] [Google Scholar]
  45. Koranyi L., James D., Mueckler M., Permutt M. A. Glucose transporter levels in spontaneously obese (db/db) insulin-resistant mice. J Clin Invest. 1990 Mar;85(3):962–967. doi: 10.1172/JCI114526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Kusari J., Verma U. S., Buse J. B., Henry R. R., Olefsky J. M. Analysis of the gene sequences of the insulin receptor and the insulin-sensitive glucose transporter (GLUT-4) in patients with common-type non-insulin-dependent diabetes mellitus. J Clin Invest. 1991 Oct;88(4):1323–1330. doi: 10.1172/JCI115437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Le Marchand-Brustel Y., Freychet P. Effect of fasting and streptozotocin diabetes on insulin binding and action in the isolated mouse soleus muscle. J Clin Invest. 1979 Nov;64(5):1505–1515. doi: 10.1172/JCI109609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Manson J. E., Rimm E. B., Stampfer M. J., Colditz G. A., Willett W. C., Krolewski A. S., Rosner B., Hennekens C. H., Speizer F. E. Physical activity and incidence of non-insulin-dependent diabetes mellitus in women. Lancet. 1991 Sep 28;338(8770):774–778. doi: 10.1016/0140-6736(91)90664-b. [DOI] [PubMed] [Google Scholar]
  49. Mueckler M. Family of glucose-transporter genes. Implications for glucose homeostasis and diabetes. Diabetes. 1990 Jan;39(1):6–11. doi: 10.2337/diacare.39.1.6. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. Pedersen O., Bak J. F., Andersen P. H., Lund S., Moller D. E., Flier J. S., Kahn B. B. Evidence against altered expression of GLUT1 or GLUT4 in skeletal muscle of patients with obesity or NIDDM. Diabetes. 1990 Jul;39(7):865–870. doi: 10.2337/diab.39.7.865. [DOI] [PubMed] [Google Scholar]
  52. Pedersen O., Kahn C. R., Flier J. S., Kahn B. B. High fat feeding causes insulin resistance and a marked decrease in the expression of glucose transporters (Glut 4) in fat cells of rats. Endocrinology. 1991 Aug;129(2):771–777. doi: 10.1210/endo-129-2-771. [DOI] [PubMed] [Google Scholar]
  53. Piper R. C., Hess L. J., James D. E. Differential sorting of two glucose transporters expressed in insulin-sensitive cells. Am J Physiol. 1991 Mar;260(3 Pt 1):C570–C580. doi: 10.1152/ajpcell.1991.260.3.C570. [DOI] [PubMed] [Google Scholar]
  54. Ploug T., Stallknecht B. M., Pedersen O., Kahn B. B., Ohkuwa T., Vinten J., Galbo H. Effect of endurance training on glucose transport capacity and glucose transporter expression in rat skeletal muscle. Am J Physiol. 1990 Dec;259(6 Pt 1):E778–E786. doi: 10.1152/ajpendo.1990.259.6.E778. [DOI] [PubMed] [Google Scholar]
  55. Richardson J. M., Balon T. W., Treadway J. L., Pessin J. E. Differential regulation of glucose transporter activity and expression in red and white skeletal muscle. J Biol Chem. 1991 Jul 5;266(19):12690–12694. [PubMed] [Google Scholar]
  56. Scarlett J. A., Kolterman O. G., Ciaraldi T. P., Kao M., Olefsky J. M. Insulin treatment reverses the postreceptor defect in adipocyte 3-O-methylglucose transport in type II diabetes mellitus. J Clin Endocrinol Metab. 1983 Jun;56(6):1195–1201. doi: 10.1210/jcem-56-6-1195. [DOI] [PubMed] [Google Scholar]
  57. Simpson I. A., Cushman S. W. Hormonal regulation of mammalian glucose transport. Annu Rev Biochem. 1986;55:1059–1089. doi: 10.1146/annurev.bi.55.070186.005211. [DOI] [PubMed] [Google Scholar]
  58. Sinha M. K., Raineri-Maldonado C., Buchanan C., Pories W. J., Carter-Su C., Pilch P. F., Caro J. F. Adipose tissue glucose transporters in NIDDM. Decreased levels of muscle/fat isoform. Diabetes. 1991 Apr;40(4):472–477. doi: 10.2337/diab.40.4.472. [DOI] [PubMed] [Google Scholar]
  59. Sivitz W. I., DeSautel S. L., Kayano T., Bell G. I., Pessin J. E. Regulation of glucose transporter messenger RNA in insulin-deficient states. Nature. 1989 Jul 6;340(6228):72–74. doi: 10.1038/340072a0. [DOI] [PubMed] [Google Scholar]
  60. Slot J. W., Geuze H. J., Gigengack S., James D. E., Lienhard G. E. Translocation of the glucose transporter GLUT4 in cardiac myocytes of the rat. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7815–7819. doi: 10.1073/pnas.88.17.7815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Slot J. W., Geuze H. J., Gigengack S., Lienhard G. E., James D. E. Immuno-localization of the insulin regulatable glucose transporter in brown adipose tissue of the rat. J Cell Biol. 1991 Apr;113(1):123–135. doi: 10.1083/jcb.113.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Tal M., Kahn B. B., Lodish H. F. Expression of the low Km GLUT-1 glucose transporter is turned on in perivenous hepatocytes of insulin-deficient diabetic rats. Endocrinology. 1991 Oct;129(4):1933–1941. doi: 10.1210/endo-129-4-1933. [DOI] [PubMed] [Google Scholar]
  63. Thorens B., Charron M. J., Lodish H. F. Molecular physiology of glucose transporters. Diabetes Care. 1990 Mar;13(3):209–218. doi: 10.2337/diacare.13.3.209. [DOI] [PubMed] [Google Scholar]
  64. Thorens B., Flier J. S., Lodish H. F., Kahn B. B. Differential regulation of two glucose transporters in rat liver by fasting and refeeding and by diabetes and insulin treatment. Diabetes. 1990 Jun;39(6):712–719. doi: 10.2337/diab.39.6.712. [DOI] [PubMed] [Google Scholar]
  65. Thorens B., Lodish H. F., Brown D. Differential localization of two glucose transporter isoforms in rat kidney. Am J Physiol. 1990 Dec;259(6 Pt 1):C286–C294. doi: 10.1152/ajpcell.1990.259.2.C286. [DOI] [PubMed] [Google Scholar]
  66. Thorens B., Weir G. C., Leahy J. L., Lodish H. F., Bonner-Weir S. Reduced expression of the liver/beta-cell glucose transporter isoform in glucose-insensitive pancreatic beta cells of diabetic rats. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6492–6496. doi: 10.1073/pnas.87.17.6492. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Turk E., Zabel B., Mundlos S., Dyer J., Wright E. M. Glucose/galactose malabsorption caused by a defect in the Na+/glucose cotransporter. Nature. 1991 Mar 28;350(6316):354–356. doi: 10.1038/350354a0. [DOI] [PubMed] [Google Scholar]
  68. Unger R. H. Diabetic hyperglycemia: link to impaired glucose transport in pancreatic beta cells. Science. 1991 Mar 8;251(4998):1200–1205. doi: 10.1126/science.2006409. [DOI] [PubMed] [Google Scholar]
  69. Wallberg-Henriksson H., Zetan N., Henriksson J. Reversibility of decreased insulin-stimulated glucose transport capacity in diabetic muscle with in vitro incubation. Insulin is not required. J Biol Chem. 1987 Jun 5;262(16):7665–7671. [PubMed] [Google Scholar]
  70. Wright E. M., Turk E., Zabel B., Mundlos S., Dyer J. Molecular genetics of intestinal glucose transport. J Clin Invest. 1991 Nov;88(5):1435–1440. doi: 10.1172/JCI115451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Zorzano A., Wilkinson W., Kotliar N., Thoidis G., Wadzinkski B. E., Ruoho A. E., Pilch P. F. Insulin-regulated glucose uptake in rat adipocytes is mediated by two transporter isoforms present in at least two vesicle populations. J Biol Chem. 1989 Jul 25;264(21):12358–12363. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES