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Insulin, Insulin-like Growth Factors, and Their Receptors in the Central Nervous System pp 1–10Cite as

Internalization of Insulin and Its Receptor: Role in Signaling

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Abstract

Tissue resistance to the action of insulin plays a role in the pathogenesis of Diabetes Mellitus, especially the Type II variety.1 This has given clinical relevance to investigation of the mechanism of insulin action on target tissues. One approach to studying insulin action is to examine the nature of its interaction with target cells. In this article we shall briefly outline the fate of insulin following interaction with its receptor, and the role that subsequent cellular handling of insulin-receptor complexes might play in hormone signal transmission.

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References

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

    Article  PubMed  CAS  Google Scholar 

  2. Y. Schecter, J. Schlessinger, S. Jacobs, K.-J. Chang, and P. 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 (1978).

    Article  Google Scholar 

  3. B. I. Posner, J. J. M. Bergeron, Z. Josefsberg, M. N. Khan, R. J. Khan, B. A. Patel, R. A. Sikstrom, and A. K. Verma, Polypeptide Hormones: Intracellular receptors and internalization, Recent Prog. Horm. Res. 37: 539 (1981).

    PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. J. J. M. Bergeron, J. Cruz, M. N. Khan, and B. I. Posner, Uptake of insulin and other ligands into receptor-rich endocytic components of target cells. The endosomal apparatus, Annual Rev. of Phvsiol. 47: 383 (1985).

    Article  Google Scholar 

  6. J. J. M. Bergeron, R. Sikstrom, A. R. Hand and B. I. Posner, Binding and uptake of 125I-insulin into rat liver hepatocytes and endothelium: An in vivo radioautographic study, J. Cell Biol. 80: 427 (1979).

    Article  PubMed  CAS  Google Scholar 

  7. B. I. Posner, B. Patel, M. N. Khan, and J. J. M. Bergeron, Effect of chloro- quine on the internalization of 125I-insulin into subcellular fractions of rat liver: Evidence for an effect of chloroquine on Golgi elements, J. Biol. Chem. 257: 5789 (1982).

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  9. A. D. Attie, R. C. Pittman, and D. Steinberg, Hepatic catabolism of low density lipoprotein: Mechanisms and metabolic consequences, Heoatologv 2: 269 (1982).

    CAS  Google Scholar 

  10. 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 (1984).

    Article  PubMed  CAS  Google Scholar 

  11. D. G. Kay, M. N. Khan, B. I. Posner, and J. J. M. Bergeron, 125I-insulin in hepatic Golgi fractions: Application of the diaminobenzidine (DAB)-shift protocol, Biochem. Bioohvs Res. Commun. 123: 1144 (1984).

    Article  CAS  Google Scholar 

  12. A. Helenius, J. Mellman, D. Wall, and A. Hubbard, Endosomes, Trends Biochem. Scis 7: 245 (1983).

    Article  Google Scholar 

  13. M. N. Khan, S. Savoie, J. J. M. Bergeron, and B. I. Posner, Insulin and insulin receptor uptake into Golgi fractions: Effect and possible site of chloro- quine action, Diabetes 34: 1025 (1985).

    Article  PubMed  CAS  Google Scholar 

  14. H. J. Geuze, J. W. Slot, G. J. A. M. Strous, H. F. Lodish, and A. L. Schwartz, Intracellular site of asialoglycoprotein receptor-mediated endocytosis, Cell 32: 277 (1983).

    Article  PubMed  CAS  Google Scholar 

  15. Z. Josefsberg, B. I. Posner, B. Patel, and J. J. M. Bergeron, Uptake of prolactin into female rat liver: Concentration of intact hormone in the Golgi apparatus, J. Biol. Chem. 254: 209 (1979).

    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 (1982).

    Article  PubMed  CAS  Google Scholar 

  17. 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 (1981).

    PubMed  CAS  Google Scholar 

  18. 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 (1982).

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  20. V. Pezzino, R. Vigneri, N. B. Pliam, and I. D. Goldfine, Rapid regulation of plasma membrane insulin receptors, Diabetologia 29: 211 (1980).

    Article  Google Scholar 

  21. H. 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 (1984).

    Article  PubMed  CAS  Google Scholar 

  22. W. S. May, Jr. and P. Cuatrecasas, Transferrin receptor: Its biological significance, J, Membr. Biol. 88: 205 (1985).

    Article  CAS  Google Scholar 

  23. D. R. Abrahamson and R. Rodewald, Evidence for the sorting of endocytic vesicle contents during the receptor-mediated transport of IgG across the newborn rat intestine, J. Cell Biol. 91: 270 (1981).

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  25. R. Walsh, F. J. Slaku and B. I. Posner, Prolactin transport from blood to CSF: A specific receptor-mediated mechanism, Endocrinology (in press).

    Google Scholar 

  26. S. Terris, and D. F. Steiner, Binding and degradation of 125I-insulin by rat hepatocytes, J.Biol. Chem. 250: 8389 (1975).

    PubMed  CAS  Google Scholar 

  27. R. J. Khan, M. N. Khan, J. J. M. Bergeron, and B. I. Posner, Prolactin uptake into liver endocytic components: Reduced sensitivity to chloroquine, Biochim, Bioohvs. Acta 838: 77 (1985).

    Article  CAS  Google Scholar 

  28. B. I. Posner, Z. Josefsberg, and J. J. M. Bergeron, Intracellular polypeptide hormone receptors: Characterization and induction of prolactin receptors in the Golgi apparatus of rat liver, J. Biol. Chem, 254: 12494 (1979).

    PubMed  CAS  Google Scholar 

  29. J. J. M. Bergeron, N. Searle, M. N. Khan, and B. I. Posner, Differential and analytical subfractionation of rat liver components internalizing insulin and prolactin, Biochemistry 25: 1756 (1986).

    Article  PubMed  CAS  Google Scholar 

  30. M. N. Khan, S. Savoie, J. J. M. Bergeron, and B. I. Posner, Differential kinetics and sensitivity to chloroquine for receptor-mediated insulin and prolactin endocytosis in liver parenchymal cells, Biochim. Bioohvs. Acta 888: 100 (1986).

    Article  CAS  Google Scholar 

  31. S. Diment and P. Stahl, Macrophage endosomes contain protease which degrade endocytosed protein ligands, J. Biol. Chem. 260: 15311 (1985).

    PubMed  CAS  Google Scholar 

  32. H. J. Geuze, J. W. Slot, G. J. A. M. Strous, A. Hasilik, and K. von Figura, Possible pathways for lysosomal enzyme delivery, J. Cell Biol. 101: 2253 (1985).

    Article  PubMed  CAS  Google Scholar 

  33. R. J. Pease, G. D. Smith, and T. J. Peters, Degradation of endocytosed insulin in rat liver is mediated by low-density vesicles, Biochem. J. 228: 137 (1985).

    PubMed  CAS  Google Scholar 

  34. F. G. Hamel, B. I. Posner, M. Vanderwel, J. J. M. Bergeron, and W. C. Duckworth, Insulin degradation by endosomes in intact liver, Abstract, Forty seventh Annual Meeting of the American Diabetes Association, Diabetes (submitted).

    Google Scholar 

  35. K. Kikuchi, J. Lamer, R. J. Freer, and A. R. Day, Effect of insulin fragments on biological activity of insulin and desoctapeptide insulin, I. Potentiation of biological activities, J. Biol. Chem. 256: 9441 (1981).

    PubMed  CAS  Google Scholar 

  36. A. R. Saltiel, J. A. Fox, P. Sherline, and P. Cuatrecasas, Insulin-stimulated hydrolysis of a novel glycolipid generates modulators of cAMP phosphodiesterase, Science 233: 967 (1986).

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  38. O. M. Rosen, R. Herrera, Y. Olowe, L. M. Petruzzelli, and M. H. Cobb, Phosphorylation activates the insulin receptor tyrosine protein kinase, Proc. Natl. Acad. Sci. USA 80: 3237 (1983).

    Article  PubMed  CAS  Google Scholar 

  39. M. N. Khan, S. Savoie, J. J. M. Bergeron, and B. I. Posner, Characterization of rat liver endosomal fractions: in vivo activation of insulin-stimulable kinase in these structures, J. Biol. Chem. 261: 8462 (1986).

    PubMed  CAS  Google Scholar 

  40. M. N. Khan, J. J. M. Bergeron, and B. I. Posner, Internalization of the activated insulin receptor kinase in rat liver endosomes, J. Cell. Biol. 103 (No.5, Part 2): 450a (1986). [Abstr. No. 1679 ].

    Google Scholar 

  41. G. Grunberger, Y. Zick, and P. Gorden, Defect in phosphorylation of insulin receptors in cells from an insulin-resistant patient with normal insulin binding, Science 223: 932 (1984).

    Article  PubMed  CAS  Google Scholar 

  42. D. O. Morgan, L. Ho, L. J. Korn, and R. A. Roth, Insulin action is blocked by a monoclonal antibody that inhibits the insulin-receptor kinase, Proc. Natl. Acad. Sci. USA 83: 328 (1986).

    Article  PubMed  CAS  Google Scholar 

  43. L. Ellis, E. Clauser, D. O. Morgan, M. Edery, R. A. Roth, and W. J. Rutter, Replacement of insulin receptor tyrosine residues 1162 and 1163 compromises insulin-stimulated kinase activity and uptake of 2-deoxyglucose, Cell 45: 721 (1986).

    Article  PubMed  CAS  Google Scholar 

  44. S. Kadota, I. G. Fantus, H. Guyda, and B. Posner, Vanadate augments adipocyte IGF-2 binding in a manner similar but not identical to insulin, Diabetes 35 (Suppl. 1): 53A (1986) [Abstr. No. 211].

    Google Scholar 

  45. A. L. Hubbard, D. A. Wall, and A. Ma, Isolation of rat hepatocyte plasma membranes. 1. Presence of the three major domains, J. Cell Biol. 96: 217 (1983).

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Departments of Medicine, McGill University, Montreal, Canada, H3A 1A1

    Barry I. Posner & Masood N. Khan

  2. Departments of Anatomy, McGill University, Montreal, Canada, H3A 1A1

    John J. M. Bergeron

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

Editors and Affiliations

  1. University of Florida, Gainesville, Florida, USA

    Mohan K. Raizada  & M. Ian Phillips  & 

  2. Diabetes Branch, NIDDK, NIH, Bethesda, Maryland, USA

    Derek LeRoith

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© 1987 Plenum Press, New York

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Posner, B.I., Khan, M.N., Bergeron, J.J.M. (1987). Internalization of Insulin and Its Receptor: Role in Signaling. In: Raizada, M.K., Phillips, M.I., LeRoith, D. (eds) Insulin, Insulin-like Growth Factors, and Their Receptors in the Central Nervous System. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5380-5_1

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  • DOI: https://doi.org/10.1007/978-1-4684-5380-5_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5382-9

  • Online ISBN: 978-1-4684-5380-5

  • eBook Packages: Springer Book Archive

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