Advertisement

Glucose Transporters: Overview and Implications for the Brain

  • Eddy Karnieli
  • W. Timothy Garvey

Abstract

Binding of insulin to its receptor initiates a series of biochemical events which culminate in a variety of cellular actions. In this chapter we will review some of the biochemical mechanisms underlying insulin’s ability to stimulate glucose transport in target tissues such as adipose and muscle. Furthermore, we will examine the role of the glucose transport effector system in pathophysiologic insulin-resistant states and modifications which prevent the insulin response in insulin insensitive tissues such as liver and brain.

Keywords

Glucose Transport Hexose Transport Glucose Trans Glucose Transport Activity Glucose Transport System 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Reference

  1. 1.
    Winegred, A.I. and Renold, A.E. (1958). Studies on rat adipose tissue in vitro. J. Biol. Chem. 233:267–272.Google Scholar
  2. 2.
    Crofford, O.B. and Renold, A.E. (1965). Glucose uptake by incubated rat epididymal adipose tissue. Rate limiting steps and site of insulin action. J. Biol. Chem. 240:14–21.PubMedGoogle Scholar
  3. 3.
    Crofford, O.B. and Renold, A.E. (1965). Glucose uptake by incubated rat epididymal adipose tissue. Characteristics of the glucose transport system and action of insulin. J. Biol. Chem. 240:3237–3244.PubMedGoogle Scholar
  4. 4.
    Levine R. and Goldstein, M. (1955). On the mechanism of action of insulin. Recent Prog. Horm. Res. 11:343–380.Google Scholar
  5. 5.
    Park, C.R., Reinwein, D., Henderson, M.J., Cardenas, E. and Morgan, H.E. (1959). The action of insulin on the transport of glucose through the cell membrane. Am. J. Med. 26:674–684.PubMedCrossRefGoogle Scholar
  6. 6.
    Haring, H.V., Kemmler, W., Renner, R. and Hepp, K.D. (1978). Initial lag-phase in the action of insulin on glucose transport and cAMP levels in fat cells. FEBS Lett. 95:177–180.PubMedCrossRefGoogle Scholar
  7. 7.
    Ciaraldi, T.P. and Olefsky, J.M. (1979). Coupling of insulin receptors to glucose transport: A temperature dependent time lag in activation of glucose transport. Arch. Biochem. Biophys. 193:221–231.PubMedCrossRefGoogle Scholar
  8. 8.
    Karnieli, E., Zarnowski, M.J., Hissin, P.J., Simpson, I.A., Salans, L.B. and Cushman, S.W. (1981). 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. 256:4772–4777.PubMedGoogle Scholar
  9. 9.
    Ciaraldi, T.P., and Olefsky, J.M. (1980). Relationship between deactivation of insulin stimulated glucose transport and insulin dissociation in isolated rat adipocytes. J. Biol. Chem. 255:327–330.PubMedGoogle Scholar
  10. 10.
    Vinten, J., Gliemann, J. and Osterlind, K. (1976). Exchange of 3–0methylglucose in isolated fat cells: Concentration dependence and effect of insulin. J. Biol.. Chem. 251:794–800.PubMedGoogle Scholar
  11. 11.
    Wardzala, L.J., Cushman, S.W., and Salans, L.B. (1978). Mechanism of insulin action on glucose transport in the isolated rat adipose cell. J. Biol. Chem. 253:8002–8005.PubMedGoogle Scholar
  12. 12.
    Olefsky, J.M. (1978). Mechanisms of the ability of insulin to activate the glucose transport system in rat adipocytes. Biochem. J. 172:137–145.PubMedGoogle Scholar
  13. 13.
    Whitesell, R.R., and Gliemann, J. (1979). Kientic parameters of transport of 3–0-methylglucose and glucose in adipocytes. J. Biol. Chem. 245:5276–5286.Google Scholar
  14. 14.
    Whitesell, R.R., and Abumrad, N.A. (1985). Increased affinity predominates in insulin stimulation of glucose transport in the adipocyte. J. Biol. Chem. 260:2984–2899.Google Scholar
  15. 15.
    Martin, D.B., and Carter, J.R. (1970). Insulin stimulated glucose uptake by subcellular particles from adipose tissue. Science 67:873–874.CrossRefGoogle Scholar
  16. 16.
    McKeel, D.W., and Jarret, L. (1970). Preparation and characterization of plasma membrane fractions from isolated fat cell. J. Cell Biol. 44:417–432.PubMedCrossRefGoogle Scholar
  17. 17.
    Cushman, S.W., and Wardzala, L.J. (1980). Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell: apparent translocation of intracellular transport systems to the plasma membrane. J. Biol. Chem. 255:4758–4662.PubMedGoogle Scholar
  18. 18.
    Suzuki, K., and Kono, T. (1980). Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site. Proc. Natl. Acad. Sci. USA. 77:2542–2545.PubMedCrossRefGoogle Scholar
  19. 19.
    Simpson, I.A., Yver, D.R., Hissin, P.J., Wardzala, L.J., Karnieli, E., Salans, L.B., and Cushman, S.W. (1983b). Insulin-stimulated translocation of glucose transporters in the isolated rat adipose cell: characterization of subcellular fractions. Biochim. Biophys. Acta. 763:393–407.CrossRefGoogle Scholar
  20. 20.
    Kono, T., Suzuki, K., Dansey, L.E., Robinson, F.W., and Blevins, T.L. (1981). Energy-dependent and protein synthesis-independent recycling of the insulin-sensitive glucose transport mechanism in fat cells. J. Biol. Chem. 256:6400–6407.PubMedGoogle Scholar
  21. 21.
    Toyoda, N., Robinson, F.W., Smith, M.M., Flanagan, J.E., and Kono, T. (1986). Apparent translocation of glucose transport activity in rat epididimal adipocytes by insulin-like effects of high pH or hyperosmolarity. J. Biol. Chem. 261:2117–2122.PubMedGoogle Scholar
  22. 22.
    Wheeler, T.J., Simpson, I.A., Sogin, D.C., Hinkle, P.C., and Cushman, S.W. (1982). Detection of the rat adipocyte glucose transporter with an antibody against the human red cell glucose transporter. Biochem. Biophys. Res. Commun. 105:89–95.PubMedCrossRefGoogle Scholar
  23. 23.
    Wardzala, L.J., and Jeanrenaud, B. (1981). Potential mechanism of insulin action on glucose transport in isolated rat diaphragm. Apparent translocation of intracellular transport untis to the plasma membrane. J. Biol. Chem. 256:7090–7093.PubMedGoogle Scholar
  24. 24.
    Wardzala, L.J., and Jeanrenaud, B. (1983). Identification of D-glucose inhibitable cytochalasin-B binding site as the glucose transporter in rat diaphragm plasma and microsomal membranes. Biochim. Biophys. Acta 730:49.PubMedCrossRefGoogle Scholar
  25. 25.
    Watanabe, T., Smith, M.M., Robinson, F.W., and Kono, T. (1984). Insulin action on glucose transport in cardiac muscle. J. Biol. Chem. 259:13117–13122.PubMedGoogle Scholar
  26. 26.
    Karnieli, E., Brazilai, A., Rafaeloff, R. and Armoni, M. (1986). Distribution of glucose transporters in membrane fractions isolated from human adipose cells: relation to cell size. J. Clin. Invest. 78:1051–1055.PubMedCrossRefGoogle Scholar
  27. 27.
    Oka, Y., and Czech, M.P. (1984). Photoaffinity labeling of insulin-sensitive hexose transporters in intact rat adipocytes: direct evidence that laten transporters become exposed to the extracellular pace in response to insulin. J. Biol. Chem. 259:8125–8133.PubMedGoogle Scholar
  28. 28.
    Horuk, R., Matthaei, S., Olefsky, J.M., Baly, D.L., Cushman, S.W., and Simpson, I.A. (1986). Biochemical and functional heterogeneity of rat adipocyte glucose transporters. J. Biol. Chem. 261:1823–1828.PubMedGoogle Scholar
  29. 29.
    Matthaei, S., Garvey, W.T., Horuk, R., Hueckstaedt, T.P., and Olefsky, J.M. (1987). The human adipocyte glucose transport system: biochemical and functional heterogeneity of hexose carriers. J. Clin. Invest. In press.Google Scholar
  30. 30.
    Mueckler, M., Caruso, C., Baldwin, S.A., Panico, M., Blench, I., Morris, H.R., Allard, W.J., Lienhard, G.E., and Lodish, H.F. (1985). Sequence and structure of a human glucose transporter. Science 229:941–945.PubMedCrossRefGoogle Scholar
  31. 31.
    Birnbaum, M.J., Haspel, H.C., and Rosen, O.M. (1986). Cloning and characterization of a cDNA endoding the rat brain glucose transporter protein. Proc. Natl. Acad. Sci. USA. 83:5784–5788.PubMedCrossRefGoogle Scholar
  32. 32.
    Haspel, H.C., Birnbaum, M.J., Wilk, e.W., and Rosen, O.M. (1985). Biosynthesis precursors and in vitro translation products of the glucose transporter of human hepatocarcinoma cells, human fibroblasts, and murine preadipocytes. J. Biol. Chem. 260:7219–7225.PubMedGoogle Scholar
  33. 33.
    Gorge, F.R., Baldwin, S.A., and Leinhard, G.E. (1979). The monosaccharide transporter from human erythrocytes is heterogeneously glycosylated. Biochem. Biophys. Res. Commun. 91:955–961.CrossRefGoogle Scholar
  34. 34.
    Shanahan, M.F., Olson, S.A., Weber, M.J., Lienhard, G.E., and Gorga, J.C. (1982). Photolabeling of glucose-sensitive cytochalasin B binding proteins in erythrocyte, fibroblast and adipocyte membranes. Biochem. Biophys. Res. Commun. 107:38–43.PubMedCrossRefGoogle Scholar
  35. 35.
    Witters, L.A., Vater, C.A., and Lienhard, G.E. (1985). Phosphorylation of the glucose transporter in vitro, and in vivo by protein kinase C. Nature 315:777–778.PubMedCrossRefGoogle Scholar
  36. 36.
    Smith, U., Karoda, M. and Simpson, I.A. (1984) Counter-regulation of insulin-stimulated glucose transport by cathechalamines in the isolated rat adipose cell. J. Biol. Chem. 259:8758–8763.PubMedGoogle Scholar
  37. 37.
    Karnieli, E., Armoni, M., Cohen, P., Kanter, Y., and Rafaeloff, R. (1987). Reversal of insulin resistance in diabetic rat adipocytes by insulin therapy: restoration of the pool of glucose transporters and enhancement of glucose’ transport activity. Diabetes. In press.Google Scholar
  38. 38.
    Rafaeloff, R., Armoni, A., and Karnieli, E. (1986) Insulin therapy manipulates the affinity of glucose transporters in adipocytes isolated from diabetic rats. Diabetes 35(Suppl. 1):79A (Abstr).Google Scholar
  39. 39.
    Karnieli, E., R. Moscona, B. Hirshovitz, Y. Illouz, R. Rafaeloff, and M. Armoni. (1986). Discrepancy between glucose transport and transporters in subcutaneous human adipocytes. Diabetes 35(Suppl. 2):52A (Abstr).Google Scholar
  40. 40.
    Kono, T. (1983). Recycling of insulin-sensitive glucose transporter in rat adipocytes. Methods in Enzymology 98:431–444.PubMedCrossRefGoogle Scholar
  41. 41.
    Haspel, H.C., Wilk, E.W., Birnbaum, M.J., Cushman, S.W., and Rosen, O.M. (1986). Glucose deprivation and hexose transporter polypeptides of murine fibroblasts. J. Biol. Chem. 261:6778–6789PubMedGoogle Scholar
  42. 42.
    Reaven, G.M., Bernstein, R., Davis, B., and Olefsky, J.M. (1976). Non-ketotic diabetes mellitus: Insulin deficiency or insulin resistance? Am. J. Med. 60:80–88.PubMedCrossRefGoogle Scholar
  43. 43.
    Kolterman, O.G., Gray, R.S., Griffin, J., Burstein, P., Insel, J., Scarlett, J.A., and Olefsky, J.M. (1981). Receptor and post-receptor defects contribute to the insulin resistance in non-insulin dependent diabetes mellitus. J. Clin. Invest. 68:957–969.PubMedCrossRefGoogle Scholar
  44. 44.
    Rizza, R.A., Mandarino, L.J., and Gerich, J.E. (1981). Mechanisms of insulin resistance in man: Assessment using the insulin dose response curve in conjunction with insulin receptor binding. Am. J. Med. 70:169–176.PubMedCrossRefGoogle Scholar
  45. 45.
    Ciaraldi, T.P., Kolterman, O.G., Scarlett, J.A., Kao, M., and Olefsky, J.M. (1982). Role of the glucose transport system in the post-receptor defect of non-insulin dependent diabetes mellitus. Diabetes 31:1016–1022.PubMedGoogle Scholar
  46. 46.
    Kashiwagi, A., Verso, M.A., Andrews, J., Vasquez, B., Reaven, G., and Foley, J.E. (1983). In vitro insulin resistance of human adipocytes isolated from subjects with noninsulin-dependent diabetes mellitus. J. clin. Invest. 72:1246–1254.PubMedCrossRefGoogle Scholar
  47. 47.
    Scarlett, J.A., Kolterman, O.G., Ciaraldi, T.P., Kao, M., and Olefsky, J.M. (1983). Insulin treatment reverses the post-receptor defect in adipocyte 3–0-methyl glucose transport in Type II diabetes mellitus. J. Clin. Endocrinol. Metab. 56:1195–1201.PubMedCrossRefGoogle Scholar
  48. 48.
    Foley, J.E., Kashiwagi, A., Verso, M.A., Reaven, G., and Andrews, J. (1983). Improvement in in vitro insulin action after one month of insulin therapy in obvese non insulin-dependent diabetes. J. Clin. Invest. 72:1901–1909.PubMedCrossRefGoogle Scholar
  49. 49.
    Garvey, W.T., Olefsky, J.M., Griffin, J., Hamman, R.F., and Kolterman, O.G. (1985). The effect of insulin treatment on insulin secretion and insulin actionin Type II diabetes mellitus. Diabetes 34:222–234.PubMedCrossRefGoogle Scholar
  50. 50.
    Scarlett, J.A., Gray, R.S., Griffin, J., Olefsky, J.M., and Kolterman, O.G. (1982). Insulin treatment reverses the insulin resistance of Type II diabetes mellitus. Diabetes Care 5:353–363.PubMedGoogle Scholar
  51. 51.
    Andrews, W.J., Vasquez, B., Nagulesparan, M., Klimes, I., Foley, J.E., and Unger, R. (1984). Insulin therapy in obese NIDDM induces improvements in insulin action and secretion that are maintained for two weeks after insulin withdrawal. Diabetes 33:634–642.PubMedCrossRefGoogle Scholar
  52. 52.
    Hjollund E., Pederson, O., Richelsen, B., Beck-Nielsen, H., and Schwartz, S.N. (1985). Glucose transport and metabolism in adipocytes from newly diagnosed untreated insulin-dependent diabetics: severly impaired basal and post insulin binding activities. J. Clin. Invest. 76:2091–2096.PubMedCrossRefGoogle Scholar
  53. 53.
    Kobayashi, M., Olefsky, J.M. (1979). Effects of streptozotocininduced diabetes on insulin binding, glucose transport, and intracellular glucose metabolism in isolated rat adipocytes. Diabetes 28:87–95.PubMedGoogle Scholar
  54. 54.
    Karnieli, E., Hissin, P.J., Simpson, I.A., Salans, L.B., and Cushman, W. (1981). A possible mechanism of insulin resistance in the rat adipose cell in streptozotozin-induced diabetes mellitus. Depletion of intracellular glucose transport systems. J. Clin. Invest. 68:811–814.PubMedCrossRefGoogle Scholar
  55. 55.
    Hissin, P.J., Karnieli, E., Simpson, I.A., Salans, L.B., and Cushman, S.W. (1982). A possible mechanism of insulin resistance in the rat adipose cell with high fat/low carbohydrate feeding. Depletion of intracellular glucose transport systems. Diabetes 31:589–592.PubMedCrossRefGoogle Scholar
  56. 56.
    Kahn, B.B., and Cushman, S.W. (1984). Effects of fasting and refeeding on the distribution of glucose transporters in isolated rat adipocytes. Diabetes 33(Suppl. 1):71A (abstr).Google Scholar
  57. 57.
    Garvey, W.T., Huecksteadt, T.P., and Olefsky, J.M. (1987). Role of glucose transport proteins in the insulin resistance of Type II diabetes mellitus. Clin. Res. 35:105A.Google Scholar
  58. 58.
    Armoni, M., Rafaeloff, R., Kanter, Y., Moscona, R., and Karnieli, E. (1987). The distribution of glucose transporters in NIDDM. Endocrinology 120:(abstr).Google Scholar
  59. 59.
    Karnieli, E., Lima, F.B., and Huecksteadt, T. (1987). The impact of diabetes on the intrinsic activity of glucose transporters. Diabetes 36:(Suppl 1) (abstr).Google Scholar
  60. 60.
    Hissin, P.J., Foley, J.E., Wardzala, L.J., Karnieli, E., Simpson, I.A., Salans, L.B., and Cushman, S.W. (1982). Mechanism of insulin-resistant glucose transport activity in the enlarged adipose cell of the aged obese rat. Relative depletion of intracellular glucsoe transport systems. J. Clin. Invest. 70:780–790.PubMedCrossRefGoogle Scholar
  61. 61.
    Dean, B., Peluso, I., and Harrison, L.C. (1984). A post-binding inhibitor of insulin action: increased concentrations in the plasma of non-insulin dependent diabetic subjects. Diabetes 33:450–454.PubMedCrossRefGoogle Scholar
  62. 62.
    Reaven, G.M., Sageman, W.S., Swenson, R.S. (1977). Developoment of insulin resistance in normal dogs following alloxan-induced insulin deficiency. Diabetologia 13:459–462.PubMedCrossRefGoogle Scholar
  63. 63.
    Garvey, W.T., Olefsky, J.M., and Marshall, S. (1986). Insulin induces progressive insulin resistance in cultured rat adipocytes: Sequential effects at receptor and multiple postreceptor sites. Diabetes 35:258–267.PubMedCrossRefGoogle Scholar
  64. 64.
    Garvey, W.T., Olefsky, J.M., Matthaei, S., and Marshall, S. (1987). Glucose and insulin co-regulate the transport system in primary cultured adipocytes: A new mechanism of insulin resistance. J. Biol. Chem. 262:189–197.PubMedGoogle Scholar
  65. 65.
    Van-Putten, J.P.M., and Krans, H.M.J. (1985). Glucose as a regulator of insulin-stimulated hexose transport in 3T3 adipocytes. J. Biol. Chem. 260:7996–8001.PubMedGoogle Scholar
  66. 66.
    Yamada, K., Tilloston, L.G., and Isselbacher, K.J. (1985). Regulation of hexose carriers in chick embrio fibroblasts: effects of glucose starvation and role of protein synthesis. J. Biol. Chem. 258:9786–9792.Google Scholar
  67. 67.
    Sasson, S., and Cerase, E. (1986). Substrate regulation of the glucose transport system in rat skeletal muscle: characterization and kinetic analysis in isolated soleus muscle and skeletal muscle cells in culture. J. Biol. Chem. 261:16827–16833.PubMedGoogle Scholar
  68. 68.
    Carter-Su, C., and Okamoto, K. (1985). Effect of glucocorticoids on hexose transport in rat adipocytes: evidence for decreased transporters in the plasma membrane. J. Biol. Chem. 260:11091–11098.PubMedGoogle Scholar
  69. 69.
    Zuber, M.X., Wang, S.M., Thammavaram, K.V., Reed, D.K., and Reed, B.C. (1985). Elevation of the number of cell-surface insulin receptors and the rate of 2-deoxyglucose uptake by exposure of 3T3–L1 adipocytes to tolbutamide. J. Biol. Chem. 260:14045–14052.PubMedGoogle Scholar
  70. 70.
    Jacobs, D.B., and Jung, C.Y. (1985). Sulfonylurea potentiates insulin-induced recruitment of glucose transport carrier in rat adipocytes. J. Biol. Chem. 260:2593–2596.PubMedGoogle Scholar
  71. 71.
    Wang, P.H., Beguinot, F., and Smith, R.J. (1986). Sulfonylurea effects in cultured skeletal muscle cells: Augmentation of insulin and insulin-like growth factor I and II action. Diabetes 35(Suppl. 1):53A (Abstr).Google Scholar
  72. 72.
    Scheinberg, F.P. (1965). Observation on cerebral carbohydrate metabolism in man. Ann. Int. Med. 62:367–371.PubMedGoogle Scholar
  73. 73.
    Owen, O.E., Morgan, A.P., Kemp, H.G., Sullinva, J.M., Herrera, M.G., and Cahill, G.F. (1967). Brain metabolism during fasting. J. Clin. Invest. 46:1589–1595.PubMedCrossRefGoogle Scholar
  74. 74.
    Elbrink, J., and Bihler, I. (1975). Membrane transport: its relationship to cellular metabolic rates. Science 188:1177–1184.PubMedCrossRefGoogle Scholar
  75. 75.
    Broman, T. (1941). The possibilities of the passage of substances from the blood to the central nervous system. (Is there a blood-brain barrier and a blood-cerebrospinal fluid barrier?). Acta Psychiatr. Neurol. 16:1–25.CrossRefGoogle Scholar
  76. 76.
    Brightman, M.W., and Reese, T.S. (1969). Functions between intemately apposed cell membranes in the vertebrate brain. J. Cell. Biol. 40:648–677.PubMedCrossRefGoogle Scholar
  77. 77.
    Crone, C. (1965). Facilitated transfer of glucose from blood into brain tissue. J. Physiol. London 181:103–113.PubMedGoogle Scholar
  78. 78.
    Lund-Andersen, H. (1979). Transport of glucose from blood to brain. Physiol. Rev. 59:305–352.Google Scholar
  79. 79.
    Gjedde, A. (1983). Modulation of substrate transport to the brain. Acta Neurol. Scand. 67:3–25.PubMedCrossRefGoogle Scholar
  80. 80.
    Pardridge, W.M. (1983). Brain metabolism: a perspective from the blood-brain barrier. Physiol Rev. 63:1481–1535.PubMedGoogle Scholar
  81. 81.
    Rafaelsen, O.J. (1961). Action of insulin on glucsoe uptake of rat brain slices and isolated rat cerebellium. J. Neurochem. 7:45–51.PubMedCrossRefGoogle Scholar
  82. 82.
    Buschiazzo, P.M., Terrell, E.B., and Regen, D.M. (1970). Sugar transport across the blood-brain barrier. Am. J. Physiol. 219:1505–1513.PubMedGoogle Scholar
  83. 83.
    Betz, A.L., Gillse, D.D., Yudilevich, D.L., and Drewes, L.R. (1973). Kinetics of unidirectional glucose transport into the isolated dog brain. Am. J. Physiol. 225:586–592PubMedGoogle Scholar
  84. 84.
    Goodner, C.J. and Berrie, M.A. (1977). The failure of rat hypothalamic tissue to take up labelled insulin in vivo or to respond to insulin in vitro. Endocrinol. 101:605–612.CrossRefGoogle Scholar
  85. 85.
    Hom, F.G., Goodner, C.J. and Berrie, M.A. (1984). A (3H)2-deoxyglucose method for comparing rates of glucose metabolism and insulin responses among rat tissues in vivo. Diabetes 33:141–152.PubMedCrossRefGoogle Scholar
  86. 86.
    Gorus, F.K., Hooghe-Peters, E.L., and Pipeleers, D.G. (1984). Glucose metabolism in murine fetal cortical brain cells: lack of insulin effects. J. Cell. Physiol. 121:45–50.PubMedCrossRefGoogle Scholar
  87. 87.
    Brooks, D.J., Gibbs, J.S.R., Sharp, P., Herold, S., Turton, D.R., Luthra, S.K., Kohner, E.M., Bloom, S.R., and Jones, T. (1986). Regional cerebral glucose transport in insulin-dependent diabetic patients sutided using [11C]3–0-methyl-D-glucose and positron emission tomography. J. Cereb. Blood Flow Metab. 6:240–244.PubMedCrossRefGoogle Scholar
  88. 88.
    Goldstein, G.W., Csejtey, J. and Diamond, I. (1977). Carrier mediated glucose transport in capillaries isolated from rat brain. J. Neurochem. 28:725–728.PubMedCrossRefGoogle Scholar
  89. 89.
    Betz, A.L., Csejtey, J. and Goldstein, G.W. (1979). Hexose transport and phosphorylation by capillaries isolated from rat brain. Am. J. Physiol. 236:C96–C102.PubMedGoogle Scholar
  90. 90.
    Matthaei, S., Olefsky, J.M., Garvey, W.T., and Horuk, R. (1987). Biochemical characterization and subcellular distribution of the glucose transporter from rat brain microvessels. Biochem. J., In press.Google Scholar
  91. 91.
    Havrankova, J., Roth, J., and Brownstein, M. (1978). Insulin receptors are widely distributed in the central nervous system of the rat. Nature (Lond) 272:827–829.CrossRefGoogle Scholar
  92. 92.
    Havrankova, J., Schmechel, D., Roth, J. and Brownstein, M. (1978). Identification of insulin in the brain. Proc. Natl. Acad. Sci USA 75:5737–5741.PubMedCrossRefGoogle Scholar
  93. 93.
    Haugaard, N., Vaughan, M., Haugaard, E.S., and Stadie, W.C. (1954). Studies of radioactive injected labeled insulin. J. Biol. Chem. 208:549–563.PubMedGoogle Scholar
  94. 94.
    Margoles, R.V. and Altszuler, N. (1967). Insulin in the cerebrospinal fluid. Nature (Lond) 215:1375–1376.CrossRefGoogle Scholar
  95. 95.
    Sloviter, H.A. and Yamada, H. (1971). Absence of direct action of insulin on metabolism of the isolated perfused rat brain. J. Neurochem. 18:1269–1274.PubMedCrossRefGoogle Scholar
  96. 96.
    Woods, S.C. and Porte, D. (1977). Relationship between plasma and cerebrospinal fluid insulin levels of dogs. Am. J. Physiol. 233:E331–E334.PubMedGoogle Scholar
  97. 97.
    Nelson, S.R., Schultz, D.W., Passonneau, J.V., and Lowry, O.H. (1968). Control of glycogen levels in the brain. J. Neurochem. 15:1271–1279.PubMedCrossRefGoogle Scholar
  98. 98.
    Mellerup, E.T., and Rafaelsen, O.J. (1969). Brain glycogen after ntracisternal insulin injection. J. Neurochem. 16:777–781.PubMedCrossRefGoogle Scholar
  99. 99.
    Prasannan, K.B. (1972). Effect of insulin on glucose metabolism in cerebral cortex slices under aerolic and anaerobic conditions. J. Neurochem. 19:1825–1828.PubMedCrossRefGoogle Scholar
  100. 100.
    Daniel, P.M., Love, E.R. and Pratt, O.E. (1975). Insulin and the way the brain handles glucose. J. Neurochem. 25:471–476.PubMedCrossRefGoogle Scholar
  101. 101.
    Daniel, P.M., Love, E.R. and Pratt, O.E. (1977). The influence of insulin upon the metabolism of glucose by the brain. Proc. R. Soc. London Ser. B. 196:85–104.CrossRefGoogle Scholar
  102. 102.
    Pillion, D.J., Haskell, J.F., and Meegan, E. (1982). Cerebral cortical microvessels: an insulin-sensitive tissue. Biochem. Biophys. Res. Commun. 104:686–692.PubMedCrossRefGoogle Scholar
  103. 103.
    Clarke, D.W., Boyd, F.T., Kappy, M.S., and Raizada, M.K. (1984). Insulin binds to specific receptors and stimulates 2-deoxy-D-glucose uptake in cultured glial cells from rat brain. J. Biol. Chem. 259:11672–11675.PubMedGoogle Scholar
  104. 104.
    Phillips, M.E. and Coxon, R.V. (1976). Effect of insulin and phenobarbitol on the uptake of 2-deoxyglucose by brain slices and hemidiaphragms. J. Neurochem. 27:643–645.PubMedCrossRefGoogle Scholar
  105. 105.
    Gottstein, V. (1975). The effect of insulin on cerebral glucose uptake in normal and diabetic human subjects. In Brain Work.’D.H. Ingvar and N.A. Lassen, Editors. Munksgaard, Copenhagen.Google Scholar
  106. 106.
    Hertz, M.M., Paulson, O.B., Barry, d.I., Christiansen, J.S., and Svendsen, P.A. (1981). Insulin increases glucose transfer across the blood-brain barrier in man. J. Clin. Invest. 67:597–604.PubMedCrossRefGoogle Scholar
  107. 107.
    Lund-Andersen, H. and Kjeldsen, C.S. (1977). Uptake of glucose analogues by rat brain cortex slices: membrane transport versus metabolism of 2-deoxy-D-glucose. J. Neurochem. 29:205–211.PubMedCrossRefGoogle Scholar
  108. 108.
    Heidenreich, K.A., Gilmore, P.R., and Garvey, W.T. (1987). Insulin receptors and glucose transport in primary neuronal cultures. Diabetes 36(Suppl. 1):abstract.Google Scholar
  109. 109.
    White, M.K., Bramwell, M.E. and Harris, H. (1981). Hexose transport in hybrids between malignant and normal cells. Nature 294:232–235.PubMedCrossRefGoogle Scholar
  110. 110.
    Diamond, I. and Fishman, R.A. (1973). High affinity transport and phosphorylation of 2-deoxy-D-glucose in synaptosomes. J. Neurochem. 20:1533–1542.PubMedCrossRefGoogle Scholar
  111. 111.
    Heaton, G.M. and Bachelard, H.S. (1973). The kinetic properties of hexose transport into synaptosomes from guinea pig cerebral cortex. J. Neurochem. 21:1099–1108.PubMedCrossRefGoogle Scholar
  112. 112.
    Heidenreich, K.A., Zahniser, N.R., Berhanu, P., Brandenburg, D., and Olefsky, J.M. (1984). Structural differences between insulin receptors in the brain and peripheral target tisues. J. Biol. Chem. 258:8527–8530.Google Scholar
  113. 113.
    Gammeltoft, S., Staun-Olsen, P., Ottensen, B., and Fahrenbrug, J. (1984). Insulin receptors in rat brain cortex. Kinetic evidence for a receptor subtype in central nervous system. Peptides 5:937–944PubMedCrossRefGoogle Scholar
  114. 114.
    Bergman, R.N. (1977). Integrated control of hepatic glucose metabolism. Fed. Proc. Fed. Am. Soc. Exp. Biol. 36:265–270.Google Scholar
  115. 115.
    Williams, T.F., Exton, J.H., Park, C.R., and Regen, D.M. (1968). Stereospecific transport of glucose in the perfused rat liver. Am. J. Physiol. 215:1200–1209.PubMedGoogle Scholar
  116. 116.
    Baur, H., and Heldt, H.W. (1977). Transport of hexoses across the liver-cell membrane. Eur. J. Biochem. 74:397–403.PubMedCrossRefGoogle Scholar
  117. 117.
    Ciaraldi, T.P., Horuk, R., and Matthaei, S. (1986). Biochemical and functional characterization of the rat liver glucose-transport system. Biochem. J. 240:115–123.PubMedGoogle Scholar
  118. 118.
    Dick, A.P.K., Harik, S.I., Klip, A., and Walker, D.M. (1984). Indentification and characterization of the glucose transporter of the blood-brain barrier by cytochalasin B binding and immunological reactivity. Proc. Natl. acad. Sci. USA 81:7233–7237.PubMedCrossRefGoogle Scholar
  119. 119.
    Gjedde, A. and Crone, C. (1981). Blood-brain glucose transfer: repression in chronic hyperglycemia. Science 214:456–457.PubMedCrossRefGoogle Scholar
  120. 120.
    McCall, A.L., Millington, W.R., and Wurtman, R.J. (1982). Metabolic fuel and amino acid transport into the brain in experimental diabetes mellitus. Proc. Natl. Acad. Sci. USA 79:5406–5410.PubMedCrossRefGoogle Scholar
  121. 121.
    McCall, A.L., Gould, J.B. and Ruderman, N.b. (1984). Diabetes-induced alterations of glucose metaoblism in at cerebral micro-vessels. Am. J. Physiol. 247:E462–E467.PubMedGoogle Scholar
  122. 122.
    Matthaei, S., Horuk, R., and Olefsky, J.M. (1986). Blood-brain glucose transfer in diabetes mellitus: decreased number of glucose transporters at blood-brain barrier. Diabetes 35:1181–1184PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Eddy Karnieli
    • 1
  • W. Timothy Garvey
    • 2
  1. 1.Faculty of MedicineTechnion and Rambam Medical CenterHaifaIsrael
  2. 2.Department of MedicineUniversity of California, San DiegoLa JollaUSA

Personalised recommendations