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Comparison of Type I and Type II Diabetes pp 159–173Cite as

Internalization of Insulin: Structures Involved and Significance

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 189))

Abstract

The binding of insulin to its receptor is followed by aggregation of hormone-receptor complexes and their internalization into the cell. Internalized hormone is concentrated in Golgi-enriched not lysosomal endocytotic structures which, in rat liver, contain lipoprotein particles and can be resolved by centrifugation techniques into three different entities. Recent work has shown that the bulk of endocytotic structures can be resolved from biochemically defined (i.e., galactosyltransferase-containing) Golgi elements. The endosomal apparatus or endosomes appear to function as a sorting center wherein internalized hormone-receptor complexes are concentrated and dissociated prior to directing hormone to lysosomes and receptor back to the cell surface for reutilization. Endosomes are heterogeneous and different functions might be subserved by different endosomal structures. Since an insulin stimulable receptor kinase activity can be identified in endosomes certain aspects of insulin action might be initiated herein.

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References

  1. A.D. Attie, R.C. Pittman, and D. Steinberg, Hepatic catabolism of low density lipoprotein: mechanisms and metabolic consequences, Hepatology, 2: 269–281 (1982).

    Article  PubMed  CAS  Google Scholar 

  2. S.K. Basu, J.K. Goldstein, R.G.W. Anderson, and M.S. Brown, Monensin interrupts the recycling of low density lipoprotein receptors in human fibroblasts, Cell, 24: 493–502 (1981).

    Article  PubMed  CAS  Google Scholar 

  3. J.J.M. Bergeron, J.H. Ehrenreich, P. Siekevitz, and G.E. Palade, Golgi fractions prepared from rat liver homogenates: isolation procedure and morphological characterization, J. Cell Biol, 59: 73–88 (1973).

    Article  PubMed  CAS  Google Scholar 

  4. S.J.M. Bergeron, L. Resch, R. Rachubinski, B. Patel, and B.I. Posner, Effect of colchicine on internalization of prolactin in female rat liver: an in vivo radioautographic study, J. Cell Biol, 96: 875–886 (1983).

    Article  PubMed  CAS  Google Scholar 

  5. P. Bernahu, J.H. Olefsky, P. Tsai, P. Thamm, D. Saunders, and D. Brandenburg, Internalization and molecular processing of insulin receptors in isolated rat adipocytes, Proc Natl. Acad. Sci. U.S.A. 79: 4069–4073 (1982).

    Article  Google Scholar 

  6. M.S. Brown, and J.L. Goldstein, Receptor-mediated endocytosis: insights from the lipoprotein receptor system, Proc. Natl. Acad. Sci. U.S.A. 76: 3330–3337 (1979).

    Article  PubMed  CAS  Google Scholar 

  7. Y. S. Chao, A.L. Jones, G.T. Hradek, E.E.T. Windier, and R.J. Havel, Autoradiographic localization of the sites of uptake, cellular transport, and catobolism of low density lipoproteins in the liver of normal and estrogen-treated rats, Proc. Natl. Acad. Sci. U.S.A. 78: 597–601 (1981).

    Article  PubMed  CAS  Google Scholar 

  8. P.J. Courtoy, J. Quintart, and P. Baudhuin, Shift of equilibrium density induced by 3, 3-diaminobenzidine cytochemistry: a new procedure for the analysis and purification of peroxidase-containing organelles, J. Cell Biol, 98: 870–876 (1984).

    Article  PubMed  CAS  Google Scholar 

  9. J. Cruz, B.I. Posner, and J.J.H. Bergeron, Receptor-mediated endocytosis of 125I-Insulin into pancreatic acinar cells in vivo, Endocrinology 115: 1996–2008 (1984).

    Article  PubMed  CAS  Google Scholar 

  10. R.A. Defronzo, and E. Ferrannini, The pathogenesis of noninsulin-dependent diabetes: an update, Medicine, 61: 125–140 (1982).

    Article  PubMed  CAS  Google Scholar 

  11. C. de Haen, The non-stoichiometric floating receptor model for hormone-sensitive adenylyl cyclase, J. Theor. Biol. 58: 383–400 (1976).

    Article  PubMed  Google Scholar 

  12. B. Desbuquois, S. Lopez, and H. Burlet, Ligand-induced translocation of insulin receptors in intact rat liver, J. Biol. Chem. 257: 10852–10860 (1982).

    PubMed  CAS  Google Scholar 

  13. R.B. Dickson, M.C. Willingham, and I. Pastan, a2-Macroglobulin adsorbed to colloidal gold: a new probe in the study of receptor-mediated endocytosis, J. Cell Biol, 89: 29–34 (1981).

    Article  PubMed  CAS  Google Scholar 

  14. J.H. Ehrenreich, J.J.M. Bergeron, P. Siekevitz, and G.E. Palade, Golgi fractions prepared from rat liver homogenates: isolation procedure and morphological characterization, J. Cell Biol. 59: 45–72 (1973).

    Article  PubMed  CAS  Google Scholar 

  15. C.A. Enns, J.W. Larrick, H. Suomalainen, J. Schroder, and H.H. Sussman, Co-migration and internalization of transferrin and its receptor on K562 cells, J. Cell Biol. 97: 579–585 (1983).

    Article  PubMed  CAS  Google Scholar 

  16. M. Fehlmann, J.-L. Carpentier, A. Le Cam, P. Thamm, D. Saunders, D. Brandenburg, L. Orci, and P. Freychet, Biochemical and morphological evidence that the insulin receptor is internalized with insulin in hepatocytes, J. Cell Biol. 93: 82–87 (1982).

    Article  PubMed  CAS  Google Scholar 

  17. M. Fehlmann, J.L. Carpentier, E. Van Obberghen, P. Freychet, P. Thamm, D. Saunders, D. Brandenburg, and L. Orci, Internalized insulin receptors are recycled to the cell surface in rat hepatocytes, Proc. Natl. Acad. Sci. USA, 79: 5921–5925 (1982).

    Article  PubMed  CAS  Google Scholar 

  18. H.J. Geuze, J.W. Slot, G.J.A.M. Strous, H.F. Lodish, and A.L. Schwartz, Intracellular site of asialoglycoprotein receptor-ligand uncoupling: double-label immunoelectron microscopy during receptor-mediated endocytosis, Cell 32: 277–287 (1983).

    Article  PubMed  CAS  Google Scholar 

  19. J.J. Geuze, J.W. Slot, G.J.A.M. Strous, J. Peppard, K. von Figura, A. Hasilik, and A.L. Schwartz, Intracellular receptor sorting during endocytosis: comparative immunoelectron microscopy of multiple receptors in rat liver, Cell, 37: 195–204 (1984).

    Article  PubMed  CAS  Google Scholar 

  20. P. Gorden, J.-L. Carpentier, P. Freychet, and L. Orci, Internalization of polypeptide hormones: mechanism, intracellular localization and significance, Diabetologia, 18: 263–274 (1980).

    Article  PubMed  CAS  Google Scholar 

  21. A. Green, and J.K. Olefsky, Evidence for insulin-induced internalization and degradation of insulin receptors in rat adipocytes, Proc. Natl. Acad. Sci. USA, 79: 427–431 (1982).

    Article  PubMed  CAS  Google Scholar 

  22. A. Helenius, J. Hellman, D. Wall, and A. Hubbard, Endosomes, Trends Biochem. Sci. 7: 245–250 (1983).

    Article  Google Scholar 

  23. C.R. Hopkins, Intracellular routing of transferrin and transferrin receptors in epidermoid carcinoma A431 cells, Cell, 32: 321–330 (1983).

    Article  Google Scholar 

  24. S. Jacobs, and P. Cuatrecasas, The mobile receptor hypothesis and cooperativity of hormone binding: application to insulin, Biochim. Biophys. Acta, 433: 482–495 (1976).

    Article  PubMed  CAS  Google Scholar 

  25. M. Kasuga, Y. Fujita-Yamaguchi, D.L. Blithe, H.F. White, and C.R. Kahn, Characterization of the insulin receptor kinase purified from human placental membranes, J. Biol. Chem. 258: 10973–10980 (1983).

    PubMed  CAS  Google Scholar 

  26. D.G. Kay, H.N. Khan, B.I. Posner, and J.J.K. Bergeron, 125I-insulin in hepatic Golgi fractions: application of the diaminobenzidine (DAB)-shift protocol, Biochem. Biophys. Res. Commun. 123: 1144–1148 (1984).

    Article  PubMed  CAS  Google Scholar 

  27. H.N. Khan, B.I. Posner, A.K. Verma, R.J. Khan, and J.J.H. Bergeron, Intracellular hormone receptors: evidence for insulin and lactogen receptors in a unique vesicle sedimenting in lysosome fractions of rat liver, Proc. Natl. Acad. Sci. USA, 78: 4980–4984 (1981).

    Article  PubMed  CAS  Google Scholar 

  28. H.N. Khan, B.I. Posner, R.J. Khan, and J.J.H. Bergeron, Internalization of insulin into rat liver Golgi elements: evidence for vesicle heterogeneity and the path of intracellular processing, J. Biol. Chem. 257: 5969–5976 (1982).

    PubMed  CAS  Google Scholar 

  29. H.N. Khan, S. Savoie, J.J.H. Bergeron, and B.I. Posner, Endosomes of rat liver: preparation and characterization, Abstract, Amer. Soc. Cell Biol. Meeting (1984).

    Google Scholar 

  30. R.J. Khan, M.N. Khan, J.J.M. Bergeron, and B.I. Posner, Prolactin internalization into rat differential effects of chloroquine. (in press).

    Google Scholar 

  31. K. Kikuchi, J. Lerner, R. J. insulin fragments on biological activity of insulin and desoctapeptide insulin, I. Potentiation of biological activities, J. Biol. Chem. 256: 9441–9444 (1981).

    CAS  Google Scholar 

  32. M. Krupp, and M.D. Lane, On the mechanism of ligand-induced down-regulation of insulin receptor level in the liver cell, J. Biol. Chem. 256: 1689–1694 (1981).

    PubMed  CAS  Google Scholar 

  33. L.C. Kuhn and J.P. Kraehenbuhl, The sacrificial receptor-translocation of polymeric IgA across epithelia, Trends Biochem Sci. 7: 299–302 (1982).

    Article  Google Scholar 

  34. J. Larner, G. Galasko, K. Cheng, A.A. Depaoli-Roach, L. Huang, P. Daggy and J. Kellogg, Generation by insulin of a chemical mediator that controls protein phosphorylation and dephosphorylation, Science 206: 1408–1410 (1979).

    Article  PubMed  CAS  Google Scholar 

  35. J.A. McKanna, H.T. Haigler, and S. Cohen, Hormone receptor topology and dynamics: morphological analysis using ferritinlabeled epidermal growth factor, Proc. Natl. Acad. Sci. USA 76: 5689–5693 (1979).

    Article  PubMed  CAS  Google Scholar 

  36. I.S. Hellman, H. Plutner, R.H. Steinman, J.C. Unkeless and Z.A. Cohn, J. Cell Biol. 96: 887–895 (1983).

    Article  Google Scholar 

  37. V. Pezzino, R. Vigneri, N.B. Pliam, and I.D. Goldfine, Rapid regulation of plasma membrane insulin receptors, Diabetologia 19: 211–215 (1980).

    Article  PubMed  CAS  Google Scholar 

  38. B.I. Posner, J.J.M. Bergeron, Z. Josefsberg, M.N. Khan, R.J. Khan, B.A. Patel, R.A. Sikstrom, A.K. Verma, Polypeptide hormones: intracellular receptors and internalization, Recent Prog. Norm. Res. 37: 539–582 (1981).

    Google Scholar 

  39. B.I. Posner, M.N. Khan and J.J.M. Bergeron, Endocytosis of peptide hormones and other ligands, Endocr. Revs. 3: 280–298 (1982).

    Article  CAS  Google Scholar 

  40. B.I. Posner, B. Patel, M.N. Khan, J.J.H. Bergeron, chloroquine on the internalization of 1251_ insulin cellular fractions of rat liver: evidence for an chloroquine on Golgi elements, J. Biol. Chem. 257: 5789–5799 (1982).

    PubMed  CAS  Google Scholar 

  41. G.H. Reaven, Insulin resistance in noninsulin-dependent diabetes mellitus. Does it exist and can it be measured? Amer J. Med 74 (No. 1A): 3–17 (1983)

    Article  PubMed  CAS  Google Scholar 

  42. D.-J. Reijngoud, and J.H. Tager, Chloroquine accumulation isolated rat liver lysosomes, FEBS Lett 64: 231–235 (1976).

    Article  PubMed  CAS  Google Scholar 

  43. Y. Schecter, J. Schlessinger, S. Jacobs, K-J Chang, and Cuatrecasas. Fluorescent labeling of hormone receptors in viable cells: preparation and properties of highly fluorescent derivatives of epidermal growth factor and insulin, Proc. Natl. Acad. Sci. USA 75: 2135–2139 (1978).

    Article  Google Scholar 

  44. S.J. Singer, and G.L. Nicolson, The fluid mosaic model of the structure of cell membranes, Science 175: 720–731 (1972).

    Article  PubMed  CAS  Google Scholar 

  45. G.D. Smith and T.J. Peters, The localization in rat liver of alkaline phosphodiesterase to a discrete organelle implicated in ligand internalization, Biochim. Biophys. Acta 716: 24–30 (1982).

    Article  PubMed  CAS  Google Scholar 

  46. S. Terris, and D.F. Steiner, Binding and degradation of 1251-insulin by rat hepatocytes, J. Biol. Chem. 250: 8389–8398 (1975).

    PubMed  CAS  Google Scholar 

  47. B. Tycko and F.R. Maxfield, Rapid acidification of endocytic vesicles containing a2-macroglobulin, Cell 28: 643–651 (1982).

    Article  PubMed  CAS  Google Scholar 

  48. D.A. Wall, G. Wilson, and A. Hubbard, The galactose specific recognition system of mammalian liver: the route of ligand internalization in rat hepatocytes, Cell, 21: 79–93 (1980).

    Article  PubMed  CAS  Google Scholar 

  49. R.J. Walsh, B.I. Posner, and B. Patel, Binding and uptake of 1251-iodoprolactin by epithelial cells of rat choroids plexus: an in vivo autoradiographic analysis, Endocrinology, 114: 1496–1505 (1984).

    Article  PubMed  CAS  Google Scholar 

  50. M.C. Willingham, and I. Pastan, The receptosome: an inter- mediate organelle of receptor-mediated endocytosis in cultured fibroblasts, Cell 21: 67–77 (1980).

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine, The Royal Victoria Hospital and McGill University, Montreal, Canada

    Barry I. Posner & Masood N. Kahn

  2. Department of Anatomy, The Royal Victoria Hospital and McGill University, Montreal, Canada

    John J. M. Bergeron

Authors
  1. Barry I. Posner
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  2. Masood N. Kahn
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  3. John J. M. Bergeron
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Editor information

Editors and Affiliations

  1. Departments of Physiology and Medicine and Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada

    Mladen Vranic  & George Steiner  & 

  2. Department of Medicine and Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada

    Charles H. Hollenberg

  3. Division of Endocrinology and Metabolism, Toronto General Hospital, Toronto, Canada

    George Steiner

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© 1985 Springer Science+Business Media New York

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Posner, B.I., Kahn, M.N., Bergeron, J.J.M. (1985). Internalization of Insulin: Structures Involved and Significance. In: Vranic, M., Hollenberg, C.H., Steiner, G. (eds) Comparison of Type I and Type II Diabetes. Advances in Experimental Medicine and Biology, vol 189. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1850-8_10

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  • DOI: https://doi.org/10.1007/978-1-4757-1850-8_10

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1852-2

  • Online ISBN: 978-1-4757-1850-8

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