Advertisement

Regulation of Glucose Transporters and the Na/K-ATPase by Insulin in Skeletal Muscle

  • Harinder S. Hundal
  • Amira Klip
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 334)

Abstract

In addition to its functional role of conferring bodily movement, skeletal muscle, by virtue of its total body mass also plays a key role affecting whole body metabolism. Skeletal muscle represents the chief storage site for protein (in the form of free amino acid pools and contractile muscle protein) (Rennie, 1985) and inorganic ions, notably potassium (Bergstrom et al, 1981). In the post-prandial state muscle represents the principal tissue responsible for insulin-stimulated glucose utilization (for oxidative metabolism and/or glycogen synthesis) (DeFronzo et al, 1981) and is a significant contributor in the inter-organ flow of carbon and nitrogen (in the form of muscle alanine and glutamine efflux) (Hundal, 1991). The ability to store or exclude organic and inorganic nutrients against a concentration gradient is maintained through the activity of specific membrane transport proteins as well as the selective permeability properties of the membrane. In skeletal muscle, a primary insulin target, the activation of glucose transport and Na/K transport (mediated by the Na pump or its enzymic equivalent the Na/K-ATPase) represent two of the best documented responses to the hormone (Klip et al, 1987; Klip and Paquet, 1990; Hirshman et al, 1990; Marette et al, 1992a; Erlij and Grinstein, 1976; Clausen and Kohn, 1977). The present chapter reviews work from our laboratory which has focused on the molecular basis by which insulin activates glucose transport and the Na/K-ATPase in skeletal muscle and the possible implications that regulation of these membrane processes may have during non-insulin dependent diabetes mellitus (NIDDM).

Keywords

Skeletal Muscle Human Skeletal Muscle GLUT4 Glucose Transporter Muscle Glucose Uptake Transverse Tubule 
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.

References

  1. 1.
    Baron, A.D., Brechtel, G., Wallace, P. and Edelman, S.V. 1988, Rates and tissue sites of non-insulin and insulin mediated glucose uptake in humans. Am J Physiol, 255:E769.PubMedGoogle Scholar
  2. 2.
    Bell, G.I., Kayano, T., Buse, J.B., Burant, C.F., Takeda, J., Lin, D., Fukomoto, H. and Seino, S. 1990, Molecular biology of mammalian glucose transporters. Diabetes Care, 13:198.PubMedCrossRefGoogle Scholar
  3. 3.
    Bergstrom, J., Furst, P., Holmstrom, B.O., Vinnars, E., Askanazi, J., Elwyn, D.H., Michelson, C.B.and Kinney, J.M. 1981, Influence of injury and nutrition on muscle water and electrolytes. Ann Surg, 193:810.PubMedCrossRefGoogle Scholar
  4. 4.
    Brodsky, J.L. 1990, Insulin activation of brain Na/K-ATPase is mediated by α2-form of enzyme. Am J Physiol, 258:C812.PubMedGoogle Scholar
  5. 5.
    Burant, C.F., Takeda, J., BrotLaroche, E., Bell, G.I. and Davidson, N.O. 1992, Fructose transporter in human spermatozoa and small intestine is GLUT5. J Biol Chem, 267:14523.PubMedGoogle Scholar
  6. 6.
    Clausen, T. 1985, The significance of the effects of insulin on Na, K-transport in muscle cells. In: Regulatory Peptides, pp. 59–67. Elsevier Science, Netherlands.Google Scholar
  7. 7.
    Clausen, T. and Hansen, O. 1977, Active Na-K transport and the rate of ouabain binding. The effect of insulin and other stimuli on skeletal muscle and adipocytes. J Physiol, 270:415430.Google Scholar
  8. 8.
    Clausen, T. and Kohn, P.G. 1977, The effect of insulin on the transport of sodium and potassium in rat soleus muscle. J Physiol, 254:19.Google Scholar
  9. 9.
    Cushman, S.W. and Wardzala, L.J. 1980, Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. J Biol Chem, 225:4758.Google Scholar
  10. 10.
    Daniel, P.M., Love, E.R. and Pratt, O.E. 1975, Insulin-stimulated entry of glucose into muscle in vivo as a major factor in the regulation of blood glucose. J Physiol, 247:213.Google Scholar
  11. 11.
    DeFronzo, R.A., Jacot, E., Jequier, E., Maeder, E., Wahren, J. and Felber, J.P. 1981, The effect of insulin on the disposal of intravenous glucose: Results from indirect calorimetry and hepatic and femoral venous catheterization. Diabetes, 30:1000.PubMedGoogle Scholar
  12. 12.
    DeFronzo, R.A., Gunnarsson, R., Bjorkman, O. and Wahren, J. 1985, Effect of insulin on peripheral and splanchnic glucose metabolism in non-insulin dependent (Type II) diabetes mellitus. J Clin Invest, 76:149.PubMedCrossRefGoogle Scholar
  13. 13.
    DeFronzo, R.A. 1988, The triumvirate: ß-cell, muscle, liver: a collusion responsiblc for NIDDM. Diabetes, 37:667.PubMedGoogle Scholar
  14. 14.
    Douen, A., Burdett, E., Ramlal, T., Rastogi, S., Vranic, M. and Klip, A. 1991, Characterization of glucose transporter enriched membranes from rat skeletal muscle: Assessment of endothelial cell contamination and the presence of sarcoplasmic reticulum and transverse tubules. Endocrinology, 128:611.PubMedCrossRefGoogle Scholar
  15. 15.
    Douen, A.G., Ramlal, T., Klip, A., Young, D.A., Cartee, G.D. and Holloszy, J.O. 1989, Exercise-induced increase in glucose transporters in plasma membranes of rat skeletal muscle. Endocrinology, 124:449.PubMedCrossRefGoogle Scholar
  16. 16.
    Douen, A.G., Ramlal, T., Rastogi, S., Bilan, P.J., Cartee, G.D., Vranic, M., Holloszy, J.O. and Klip, A. 1990, Exercise induces recruitment of the “insulin-responsive glucose transporter”. J Biol Chem, 265:13427.PubMedGoogle Scholar
  17. 17.
    Erlij, D. and Grinstein, S. 1976, The number of sodium ion pumping sites in skeletal muscle and its modification by insulin. J Physiol, 259:13.PubMedGoogle Scholar
  18. 18.
    Friedman, J.E., Dudek, R.W., Whitehead, D.L., Downes, D.L., Frisell, W.R., Caro, J.F. and Dohm, L. 1991, Immunolocalization of glucose transporter GLUT4 within human skeletal muscle. Diabetes, 40:150.PubMedCrossRefGoogle Scholar
  19. 19.
    Garvey, W.T., Maianu, L., Huecksteadt, T.P., Birnbaum, M.J., Molina, J.M. and Ciaraldi, T.P. 1991, Pretranslational supression of a glucose transporter protein causes insulin resistance in adipocytes from patients with non-insulin dependent diabetes mellitus and obesity. J Clin Invest, 87:1072.PubMedCrossRefGoogle Scholar
  20. 20.
    Geering, K. 1991, The functional role of the ß-subunit in the maturation and intracellular transport of Na, K-ATPase. FEBS Letters, 285:189.PubMedCrossRefGoogle Scholar
  21. 21.
    Gould, G.W. and Bell, G.I. 1990, Facilltative glucose transporters: an expanding family. TIBS, 15:18.PubMedGoogle Scholar
  22. 22.
    Grinstein, S., Rotin, D. and Mason, M.J. 1989, Na/H exchange and growth factor-induced cytosolic pH changes. Role of cellular proliferation. Biochim Biophys Acta, 988:73.PubMedCrossRefGoogle Scholar
  23. 23.
    Hirshman, M.F., Goodyear, L.J., Wardzala, L.J., Horton, E.D. and Horton, E.S. 1990, Identification of an intracellular pool of glucose transporters from basal and insulin stimulated rat skeletal muscle. J Biol Chem, 265:987.PubMedGoogle Scholar
  24. 24.
    Hundal, H.S. 1991, Role of membrane transport in the regulation of skeletal muscle glutamine turnover. Clinical Nutrition, 10(Suppl):33.PubMedCrossRefGoogle Scholar
  25. 25.
    Hundal, H.S., Ahmed, A., Guma, A., Mitsumoto, Y., Marette, A., Rennie, M.J. and Klip, A. 1992a, Biochemical and immunocytochemical localization of the “GLUT5 glucose transporter” in human skeletal muscle. Biochem J, 286:348.Google Scholar
  26. 26.
    Hundal, H.S., Marette, A., Mitsumoto, Y., Ramlal, T., Blostein, R. and Klip, A. 1992b, Tnsulin induces translocation of the α2 and β1 subunits of the Na/K-ATPase from intracellular compartments to the plasma membrane in mammalian skeletal muscle. J Biol Chem, 267: 5040.PubMedGoogle Scholar
  27. 27.
    Kahn, B.B. 1992, Alterations in glucose transporter expression and function in diabetes: mechanisms for insulin resistance. J Cell Biochem, 48:122.PubMedCrossRefGoogle Scholar
  28. 28.
    Klip, A., Ramlal, T., Young, D.A. and Holloszy, J.O. 1987, Insulin induced translocation of glucose transporters in rat hindlimb muscles. FEBS Letters, 224:224.PubMedCrossRefGoogle Scholar
  29. 29.
    Klip, A. and Leiter, L. 1990, Cellular mechanism of action of Metformin. Diabetes Care, 13:696.PubMedCrossRefGoogle Scholar
  30. 30.
    Klip, A., Ramlal, T., Bilan, P.J., Cartee, G.D., Gulve, E.A. and Holloszy, J.O. 1990, Recruitment of GLUT-4 glucose transporters by insulin in diabetic rat skeletal muscle. Biochem Biophys Res Comm, 172:728.PubMedCrossRefGoogle Scholar
  31. 31.
    Klip, A. and Marette, A. 1992, Acute and chronic signals controlling glucose transport in skeletal muscle. J Cell Biochem, 48:51.PubMedCrossRefGoogle Scholar
  32. 32.
    Klip, A. and Paquet, M. 1990, Glucose transport and glucose transporters in muscle and their metabolic regulation. Diabetes Care, 13:228.PubMedCrossRefGoogle Scholar
  33. 33.
    Liu, J.Y. and Guidotti, G. 1992, In vitro assembly of the Na/K-ATPase from subunits. J Gen Physiol, 100:135.(Abstract).Google Scholar
  34. 34.
    Lytton, J. 1985, Insulin affects the sodium affinity of rat adipocyte (Na,K)-ATPase. J Biol Chem, 260:10075.PubMedGoogle Scholar
  35. 35.
    Lytton, J., Lin, J.C. and Guidotti, G. 1985, Identification of two molecular forms of (Na,K)-ATPase in rat adipocytes: relation to insulin stimulation of the enzyme. J Biol Chem, 260: 1177.PubMedGoogle Scholar
  36. 36.
    Marette, A., Burdett, E., Douen, A.G., Vranic, M. and Klip, A. 1992a, Insulin stimulates the translocation of GLUT4 glucose transporters from a unique intracellular organelle to both the plasma membrane and transverse tubules in rat skeletal muscle. Diabetes (In press).Google Scholar
  37. 37.
    Marette, A., Hundal, H.S. and Klip, A. (1992b): Regulation of glucose transporter proteins in skeletal muscle. In: Diabetes Mellitus and Exercise, edited by J. Devlin, E.S. Horton & M. Vranic, pp. 27–43. Smith-Johnson, London.Google Scholar
  38. 38.
    McGill, D.L. and Guidotti, G. 1991, Insulin stimulates both the α1 and β2 isoforms of the rat adipocyte (Na,K) ATPase. J Biol Chem, 266:15824.PubMedGoogle Scholar
  39. 39.
    Moore, R.D. 1981, Stimulation of Na-H exchange by insulin. Biophys J, 33:203.PubMedCrossRefGoogle Scholar
  40. 40.
    Moore, R.D. 1983, Effects of insulin upon ion transport. Biochim Biophys Acta, 737:1.PubMedCrossRefGoogle Scholar
  41. 41.
    Moore, R.D., Munford, J.W. and Pillsworth, T.J. 1983, Effects of streptozotocin diabetes and fasting on intracellular Na and ATP in rat soleus muscle. J Physiol, 338:277.PubMedGoogle Scholar
  42. 42.
    Nishida, K., Ohara, T., Johnson, J., Wallner, J.S., Wilk, J., Sherman, N., Kawakami, K., Sussman, K. and Draznin, B. 1992, Na/K-ATPase activity and its αII subunit gene expression in rat skeletal muscle: Influence of diabetes, fasting and refeeding. Metabolism, 41:56.PubMedCrossRefGoogle Scholar
  43. 43.
    Omatsu-Kanbe, M. and Kitasato, H. 1990, Insulin stimulates the translocation of Na/K-dependent ATPase molecules from intracellular stores to the plasma membrane in frog skeletal muscle. Biochem J, 272:727.PubMedGoogle Scholar
  44. 44.
    Pedersen, O., Bak, J.F., Anderson, P.H., Lund, S., Moller, D.E., Flier, J.S. and Kahn, B.B. 1990, Evidence against altered expression of GLUT1 or GLUT4 in skeletal muscle of patients with obesity or NIDDM. Diabetes, 39:865.PubMedCrossRefGoogle Scholar
  45. 45.
    Ramlal, T., Rastogi, S., Vranic, M. and Klip, A. 1989, Decrease in glucose transporter number in skeletal muscle of mildly diabetic (Streptozotocin-Treated) rats. Endocrinology, 125:890.PubMedCrossRefGoogle Scholar
  46. 46.
    Rennie, M.J. 1985, Muscle protein turnover and the muscle wasting due to injury and disease. Brit Med Bull, 41:257.PubMedGoogle Scholar
  47. 47.
    Resh, M.D., Nemenoff, R.A. and Guidotti, G. 1980, Insulin stimulation of (Na,K)-Adenosine Triphosphatase-dependent 86Rb+ uptake in Rat adipocytes. J Biol Chem, 255:10938.PubMedGoogle Scholar
  48. 48.
    Rodnick, K.J., Slot, J.W., Studelska, D.R., Hanpeter, D.E., Robinson, L.J., Geuze, H.J. and James, D.E. 1992, Immunocytochemical and biochemical studies of GLUT4 in rat skeletal muscle. J Biol Chem, 267:6278.PubMedGoogle Scholar
  49. 49.
    Rosic, N.K., Standaert, M.L. and Pollet, R.J. 1985, The mechanism of insulin stimulation of (Na,K)-ATPasc transport activity in muscle. J Biol Chem, 260:6206.PubMedGoogle Scholar
  50. 50.
    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, 77:2542.PubMedCrossRefGoogle Scholar
  51. 51.
    Sweadner, K.J. 1989, Isozymes of the Na/K-ATPase. Biochim Biophys Acta, 988:185.PubMedCrossRefGoogle Scholar
  52. 52.
    Weil, E., Sasson, S. and Gutman, Y. 1991, Mechanism of insulin-induced activation of Na-K-ATPase in isolated rat solcus muscle. Am J Physiol, 261:C224.PubMedGoogle Scholar
  53. 53.
    Zierler, K.L. and Rabinowitz, D. 1964, Effect of very small concentrations of insulin on forearm metabolism. Persistence of its action on potassium and free fatty acids without its effect on glucose. J Clin Invest, 43:950.PubMedCrossRefGoogle Scholar
  54. 54.
    Zorzano, A., Wilkinson, W., Kotliar, N., Thoidis, G., Wadzinkski, B.E., Ruoho, A.E. and Pilch, P.F. 1989, Insulin-regulated glucose uptake in rat adipocytes is mediated by two transporter isoforms present in at least two vesicle populations. J Biol Chem, 264:12358.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Harinder S. Hundal
    • 1
  • Amira Klip
    • 1
  1. 1.Division of Cell BiologyThe Hospital for Sick ChildrenTorontoCanada

Personalised recommendations