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A Review of Insulin/Insulin-Like Peptide in the Central Nervous System

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Molecular Biology and Physiology of Insulin and Insulin-Like Growth Factors

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 293))

Abstract

Insulin has been demonstrated within the brain of various animal species (1). Investigations undertaken in the chick demonstrated the presence of insulin in embryonic heads prior to the development of pancreatic insulin (2). These observations prompted a search for an extra-pancreatic source of insulin production within the brain. A surge of reports were subsequently noted (3–7) including the recent observations of brain insulin-like transcripts (8–12), thereby defending a central nervous system origin of insulin. On the other hand, there has been accumulating evidence supporting the fact that circulating insulin crosses the blood-cerebro-spinal fluid (CSF) barrier and enters the CSF (13–14). Having entered the CSF, insulin was then observed to be taken up by the brain parenchyma at the circumventricular organs which lack a blood-brain barrier (15–17). Thus, there continues to be an ongoing controversy as to the exact origin of insulin within the CNS. Is it pancreatic or extra-pancreatic?

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References

  1. D. Le Roith, S.A. Hendricks, M.A. Lesniak, S. Rishi, K.L Becker, J. Havrankova, J.L. Rosenweig, M.J. Brownstein, and J. Roth, Insulin in brain and other extra–pancreatic tissues of vertebrates and non-vertebrates, Adv Metab Dis 10:303–340 (1983).

    Google Scholar 

  2. F. de Pablo, J. Roth, E. Hernandez, and R.M. Pruss, Insulin is present in chicken eggs and early chick embryos, Endocrinology 111;1909–1914 (1982).

    Article  PubMed  Google Scholar 

  3. M.K. Raizada, Localization of Insulin–like immunoreactivity in the neurons from primary cultures of rat brain, Exp Cell Res 143:351–357 (1983).

    Article  PubMed  CAS  Google Scholar 

  4. J. Havrankova, D. Schmechel, J. Roth, and M. Brownstein, Identification of insulin in rat brain, Proc Natl Acad Sci USA 75:5737–5741 (1978).

    Article  PubMed  CAS  Google Scholar 

  5. J.L. Rosenzweig, M.A. Havrankova, M.A. Lesniak, M. Brownstein, and J. Roth, Insulin is ubiquitous in extrapancreatic tissues in rats and humans, Proc Natl Acad Sci USA 77:572–576 (1980).

    Article  PubMed  CAS  Google Scholar 

  6. S.U. Devaskar, L. Karycki, and U. P. Devaskar, Varying brain insulin concentrations differentially regulate the fetal brain insulin receptors, Biochem Biophys Res Commun 136:208–219 (1986).

    Article  PubMed  CAS  Google Scholar 

  7. N. P. Birch, D.L. Christie, and A.G.C. Renwick, Immunoreactive insulin from mouse fetal brain cells in culture and whole rat brain, Biochem J 218:19–27 (1984).

    PubMed  CAS  Google Scholar 

  8. L. Villa Komaroff, A. Gonzales, H.Y. Song, B. Wentworth, and P. Dobnes, Novel insulin related sequences in fetal brain, Adv Exp Med Biol 181:65–86 (1984).

    Google Scholar 

  9. A.B. Smit, E. Vreugdenhil, R.H.M. Ebberink, W.P.M. Geraerts, J. Klootwijk, and J. Joosse, Growth–controlling molluscan neurons produce the precursor of an insulin–related peptide, Nature 331:535–538 (1988).

    Article  PubMed  CAS  Google Scholar 

  10. R. Schechter, L. Holtzclaw, F. Sadiq, A. Kahn, and S. Devaskar, Insulin synthesis by isolated neurons, Endocrinology 123:505–513 (1988).

    Article  PubMed  CAS  Google Scholar 

  11. R. Schechter, H.F. Sadiq, and S.U. Devaskar, Insulin and insulin mRNA are detected in neuronal cell cultures maintained in an insulin–free/serum–free medium, J Histochem Cytochem 38:829–836 (1990).

    Article  PubMed  CAS  Google Scholar 

  12. W.S. Young, Periventricular hypothalamic cells in the rat brain contain insulin mRNA, Neuropeptides 8:93–97 (1986).

    Article  PubMed  CAS  Google Scholar 

  13. L.J. Stein, D.M. Dorsa, D.G. Baskin, D.P. Figlewicz, H. Ikeda, S. Frankmann, M.R.C. Greenwood, D. Porte, Jr., and S.C. Woods, Immunoreactive insulin levels are elevated in the cerebrospinal fluid of genetically obese Zucker rats, Endocrinology 113:2299–2301(1983).

    Article  PubMed  CAS  Google Scholar 

  14. B.J. Wallum, J. G. Taborsky, Jr., D. Porte, Jr., D.P. Figlewicz, L. Jacobson, J. C. Beard, W.K. Ward, and D.K. Dorsa, Cerebrospinal fluid insulin levels increase during infusions in man, J Clin Endocrinol Metab 64:190–194 (1987).

    Article  PubMed  CAS  Google Scholar 

  15. D.G. Baskin, S.C. Woods, D.B. West, M. van Houten, B.I. Posner, D.M. Dorsa, and D. Porte, Jr., Immunocyto–chemical detection of insulin in rat hypothalamus and its possible uptake from cerebrospinal fluid, Endocrinology 113:1818–1825 (1983).

    Article  PubMed  CAS  Google Scholar 

  16. K.R. Duffy and W.M. Pardridge, Blood–brain barrier trancytosis of insulin in developing rabbits, Brain Res 420:32–38 (1987).

    Article  PubMed  CAS  Google Scholar 

  17. M. van Houten, B.I. Posner, B.M. Kopriwa, and J. R. Brawer, Insulin binding sites in the rat brain: In–vivo localization to the circumventricular organs by quantitative autoradiography, Endocrinology 105:666–673 (1979).

    Article  PubMed  Google Scholar 

  18. J. Havankova and J. Roth, Insulin receptors are widely distributed in the central nervous system of the rat, Nature 272:827–829 (1978).

    Article  Google Scholar 

  19. G.A. Werther, A. Hogg, B.J. Oldfield, M.J. McKinley, R. Figdor, A.M. Allen, and F.A.O. Mendelsohn, Localization and characterization of insulin receptors in rat brain and pituitary gland using in–vitro autoradiography and computerized densitometry, Endocrinology 121:1562–1570 (1987).

    Article  PubMed  CAS  Google Scholar 

  20. A.M. Moss, J.W. Linger, R.T. Moxley, and J.N. Livingston, Location of phosphotyrosine–containing proteins by immunocytochemistry in the rat forebrain corresponds to the distribution of the insulin receptor, Proc Natl Acad Sci USA 87:4453–4457 (1990).

    Article  PubMed  CAS  Google Scholar 

  21. FT. Boyd, Jr., D.W. Clarke, T.F. Muther, and M.K. Raizada, Insulin receptors and insulin modulation of norepinephrine uptake in neuronal cultures from rat brain, J Biol Chem 260: 15880–15885 (1985).

    PubMed  CAS  Google Scholar 

  22. D.G. Puro and E. Agardh, Insulin mediated regulation of neuronal maturation, Science 225:1170–1172 (1984).

    Article  PubMed  CAS  Google Scholar 

  23. S.C. Woods, D. Porte, Jr., E. Bobbioni, E. lonescu, and J.F. Sautes, Insulin: Its relationship to the central nervous system and to the control of food intake and body weight, Am J Clin Nutr 42:1063–1071 (1985).

    PubMed  CAS  Google Scholar 

  24. D.P. Figlewicz, S.C. Woods, D.G. Baskin, D.M. Dorsa, L. Wilcox, J. Stein, and D. Porte, Jr., Insulin in the central nervous system: A regulator of appetite and body weight, in: Insulin, Insulin–like Growth Factors, and Their Receptors in the Central Nervous System ,M.K. Raizada, M.I. Phillips, D. Le-Roith, eds., Plenum Press (NY and Lond.) pp 151–162 (1987).

    Chapter  Google Scholar 

  25. M. Girbau, L. Bassas, J. Alemany, and F. de Pablo, In situ autoradiography and ligand–dependent tyrosine kinase activity reveal insulin receptors and insulin–like growth factor I receptors in prepancreatic chicken embryos, Proc Natl Acad Sci USA 86:5868–5872 (1989).

    Article  PubMed  CAS  Google Scholar 

  26. L. Bassas, F. de Pablo, M.A. Lesniak, and J. Roth, Ontogeny of receptors for insulin–like peptides in chick embryo tissues: Early dominance of insulin–like growth factor over insulin receptors in brain, Endocrinology 117:2321–2329 (1985).

    Article  PubMed  CAS  Google Scholar 

  27. M. Girbau, J.A. Gomez, M.A. Lesniak, and F. de Pablo, Insulin and Insulin–like growth factor I both stimulate metabolism, growth and differentiation in the postneurula chick embryo, Endocrinology 121:1477–1482 (1987).

    Article  PubMed  CAS  Google Scholar 

  28. M.B. Harvey and P.L. Kaye, Insulin stimulates protein synthesis in compacted mouse embryos, Endocrinology 122:1182–1184 (1988).

    Article  PubMed  CAS  Google Scholar 

  29. J.P. Travers, M.K. Pratten, and F. Beck, Effects of low insulin levels on rat embryonic growth and development, Diabetes 38:773–778 (1989).

    Article  PubMed  CAS  Google Scholar 

  30. F. de Pablo, M. Girbau, J.A. Gomez, E. Hernandez, and J. Roth, Insulin antibodies retard and insulin accelerates growth and differentiation in early embryos, Diabetes 34:1063–1067 (1985).

    Article  PubMed  Google Scholar 

  31. D.S. Miller, Stimulation of RNA and protein synthesis by intracellular insulin, Science 240:506–509 (1988).

    Article  PubMed  CAS  Google Scholar 

  32. S. Heyner, L.V. Rao, L. Jarett, and R.M. Smith, Pre–implantation mouse embryos internalize maternal insulin via receptor–mediated endocytosis: Pattern of uptake and functional correlations, Dev Biol 134:48–58 (1989).

    Article  PubMed  CAS  Google Scholar 

  33. S.J. Giddings and L. Carnaghi, Rat insulin II gene expression by extraplacental membranes: A non–pancreatic source for fetal insulin, J Biol Chem 264:9462–9469 (1989).

    PubMed  CAS  Google Scholar 

  34. K. A. Heidenreich and S.P. Toledo, Insulin receptors mediate growth effects in cultured fetal neurons. I. Rapid stimulation of protein synthesis, Endocrinology 125:1451–1457 (1989).

    Article  PubMed  CAS  Google Scholar 

  35. K.A. Heidenrich, G. de Vellis, and P.R. Gilmore, Functional properties of the subtype of insulin receptor found on neurons, J Neurochem 51:878–887 (1988).

    Article  Google Scholar 

  36. E. Recio–Pinto, F.F. Lang, and D.N. Ishii, Insulin and insulin–like growth factor II permit nerve growth factor binding and the neurite formation response in cultured human neuroblastoma cells, Proc Natl Acad Sci USA 81:2562–2566 (1984).

    Article  PubMed  CAS  Google Scholar 

  37. E. DiCiccio–Bloom and I.B. Black, Insulin growth factors regulate the mitotic cycle in cultured rat sympathetic neuroblasts, Proc Natl Acad Sci USA 85:4066–4070 (1989).

    Article  Google Scholar 

  38. J. F. Mill, M.V. Chao, and D.N. Ishii, Insulin, insulin–like growth factor li, and nerve growth factor effects on tubulin mRNA levels and neurite formation, Proc Natl Acad Sci USA 82:7126–7130 (1985).

    Article  PubMed  CAS  Google Scholar 

  39. P. Fernyhough, J.F. Mill, J.L. Roberts, and D.D. Ishii, Stabilization of tubulin mRNAs by insulin and insulin–like growth factor I during neurite formation, Mol Brain Res 6:109–120 (1989).

    Article  PubMed  CAS  Google Scholar 

  40. K.A. Heidenreich, S.P. Toledo, L.L. Brunton, M.J. Watson, S. Daniel–lssakani, and B. Strulovici, Insulin stimulates the activity of a novel protein kinase C, PKC–e, in cultured fetal chick neurons, J Biol Chem 265: 15076–15082 (1990).

    PubMed  CAS  Google Scholar 

  41. K.A. Heidenreich and S.P. Toledo, Insulin receptors mediate growth effects in cultured fetal neurons. II. Activation of a protein kinase that phosphorylates ribosomal protein S6, Endocrinology 125:1458–1463 (1989).

    Article  PubMed  CAS  Google Scholar 

  42. R.W. Rees–Jones, S.A. Hendricks, M. Quarum, and J. Roth, The insulin receptor of rat brain is coupled to tyrosine kinase activity, J Biol Chem 259:3470–3474 (1984).

    PubMed  CAS  Google Scholar 

  43. W.A. Brennan, Developmental aspects of the rat brain insulin receptor: Loss of sialic acid and fluctuation in number characterize fetal development, Endocrinology 122:2364–2370 (1988).

    Article  PubMed  CAS  Google Scholar 

  44. S.U. Devaskar, N. Holekamp, L. Karycki, and U. P. Devaskar, Ontogenesis of the insulin receptor in the rabbit brain, Hormone Res 24:319–327 (1986).

    Article  PubMed  CAS  Google Scholar 

  45. K.A. Heidenreich and D. Brandenburg, Oligosaccharide heterogeneity of insulin receptors. Comparison of N–linked glycosylation of insulin receptors in adipocytes and brain, Endocrinology 118:1835–1842 (1986).

    Article  PubMed  CAS  Google Scholar 

  46. A.I. Salhanick and J.M. Amatruda, Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus, Am J Physiol 255:E173–E179 (1988).

    Google Scholar 

  47. W.L Lowe, Jr., F.T. Boyd, D.W. Clarke, M.K. Raizada, C. Hart, and D. LeRoith, Development of brain insulin receptors: Structural and functional studies of insulin receptors from whole brain and primary cell cultures, Endocrinology 119:25–35 (1986).

    Article  PubMed  CAS  Google Scholar 

  48. I. Ocrant, K.L. Valentino, L.F. Eng, R.L. Hintz, D.M. Wilson, and R.G. Rosenfeld, Structural and immunohistochemical characterization of insulin–like growth factor I and II receptors in the murine central nervous system, Endocrinology 123:1023–1034 (1988).

    Article  PubMed  CAS  Google Scholar 

  49. J. Shemer, M.K. Raizada, B.A. Masters, A. Ota, and D. LeRoith, Insulin–like growth factor I receptors in neuronal and glial cells: Characterization and biological effects in primary culture, J Biol Chem 262:7693–7699 (1987).

    PubMed  CAS  Google Scholar 

  50. D.W. Clarke, F.T. Boyd, Jr., M.S. Kappy, and M.K. Raizada, 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 (1984).

    PubMed  CAS  Google Scholar 

  51. L.M. Mudd, H. Werner, Z. Shen–Orr, C.T. Roberts, Jr., D. LeRoith, H.C. Haspel, and M.K. Raizada, Regulation of rat brain/Hep G2 glucose transporter gene expression by phorbol esters in primary cultures of neuronal and astrocytic glial cells, Endocrinology 126:545–549 (1990).

    Article  PubMed  CAS  Google Scholar 

  52. H. Werner, M.K. Raizada, L.M. Mudd, H.L. Foyt, I.A. Simpson, C.T. Roberts, Jr., and D. Le-Roith, Regulation of rat brain/Hep G2 glucose transporter gene expression by insulin and insulin–like growth factor I in primary cultures of neuronal and glial cells, Endocrinology 125:314–320 (1989).

    Article  PubMed  CAS  Google Scholar 

  53. D.W. Clarke, FT. Boyd, Jr., M.S. Kappy, and M.K. Raizada, Insulin stimulates macromolecular synthesis in cultured glial cells from rat brain, Am J Physiol 249:C484–C489 (1985).

    Google Scholar 

  54. R.P. Saneto and J. de Vellis, Hormonal regulation of the proliferation and differentiation of astrocytes and oligodendrocytes in primary culture, in: Developmental Biology of Cultured Nerve, Muscle, and Glia ,D. Schubert, ed., Vol 4: pp 125. John Wiley and Sons, New York (1984).

    Google Scholar 

  55. V.K.M. Han, J.M. Lauder, and J. D’Ercole, Characterization of somatomedin/insulin–like growth factor receptors and correlation with biologic action in cultured neonatal rat astroglial cells, J Neuroscience 7:501–511(1987).

    CAS  Google Scholar 

  56. S. Devaskar, F. Sadiq, L. Holtzclaw, and M. George, Developmental regulation of rabbit brain insulin and insulin–like growth factor receptors, J Neurochem (submitted).

    Google Scholar 

  57. D.W. Clarke, L. Mudd, FT. Boyd, M. Fields, and M.H. Raizada, Insulin is released from rat brain neuronal cells in culture, J Neurochem 47:831–836 (1986).

    Article  PubMed  CAS  Google Scholar 

  58. H.J.L. Frank and W.M. Pardridge, Insulin binding to brain microvessels, Adv Metab Disord 10:291–303 (1983).

    PubMed  CAS  Google Scholar 

  59. H.J.L. Frank, W.M. Pardridge, W.L. Morris, R.G. Rosenfeld, and T.B. Choi, Binding and internalization of insulin and insulin–like growth factors by isolated brain microvessels, Diabetes 35:654–661 (1986).

    Article  PubMed  CAS  Google Scholar 

  60. H.J.L. Frank, W.M. Pardridge, T. Jankovic–Vokes, T.J. Vinters, and W.L. Morris, Enhanced insulin binding to blood–brain barrier in vivo and to brain microvessels in vitro in newborn rabbits, Diabetes 34:728–733 (1985).

    Article  PubMed  CAS  Google Scholar 

  61. R. Schechter and S. Devaskar, Developmental regulation of insulin in the mammalian central nervous system Developmentai Brain Research (submitted 1990).

    Google Scholar 

  62. H.G. Bernstein, A. Dorn, M. Reiser, and M. Zeigler, Cerebral insulin–like immunoreactivity in rats and mice: Drastic decline during postnatal ontogenesis, Acta Histochem 74:33–36 (1984).

    Article  PubMed  CAS  Google Scholar 

  63. R. Kadle, C. Suksang, E.D. Roberson, and R.E. Fellows, Identification of an insulin–like factor in astrocyte conditioned medium, Brain Res 460:60–67 (1988).

    Article  PubMed  CAS  Google Scholar 

  64. C.G. Budd, B. Pansky, and B. Cordell, Detection of insulin synthesis in mammalian anterior pituitary cells by immunohistochemistry and demonstration of insulin related transcripts by in–situ RNA–DNA hybridization, J Histochem Cytochem 34:673–678 (1986).

    Article  PubMed  CAS  Google Scholar 

  65. V.R. Sara, C. Carlsson–Skwirut, C. Andersson, E. Hall, B. Sjogren, A. Holmgren, and H. Jornvall, Characterization of somatomedins from human fetal brain: Identification of a variant form of insulin–like growth factor I, Proc Natl Acad Sci USA 83:4904–4907 (1986).

    Article  PubMed  CAS  Google Scholar 

  66. P. Rotwein, S.K. Burgess, J.D. Milbrandt, and J.E. Krause, Differential expression of insulin–like growth factor genes in rat central nervous system, Proc Natl Acad Sci USA 85:265–269 (1988).

    Article  PubMed  CAS  Google Scholar 

  67. S.J. Giddings and L.R. Carnaghi, Selective expression of developmental regulation of the ancestral rat insulin II gene in fetal liver, Mol Endocrinol 4:1363–1369 (1990).

    Article  PubMed  CAS  Google Scholar 

  68. K. Rau, L. Muglia, and J. Locker, Insulin–gene expression in extrafetal membranes of rats, Diabetes 38:39–43 (1988).

    Article  Google Scholar 

  69. J. Paris and J.D. Richter, Maturation–specific polyadenylation and translational control: Diversity of cytoplasmic polyadenylation elements, influence of poly (A) tail size and formation of stable polyadenylation complexes, Mol Cell Biol 10:56345645 (1990).

    PubMed  CAS  Google Scholar 

  70. P.K. Lund, B.M. Moats–Staats, M.A. Hynes, J.G. Simmons, M. Jansen, A.J. D’Ercole, and J.J. Van Wyk, Somatomedin–C/lnsulin–like growth factor–l and insulin–like growth factor–ll mRNAs in rat fetal and adult tissues, J Biol Chem 261:14539–14544(1986).

    PubMed  CAS  Google Scholar 

  71. S. Devaskar and H.F. Sadiq, Regulation of neuronal insulin–like peptide, in: Molecular and Cellular Aspects of Insulin and IGF l/lI ,M.K. Raizada, ed., Plenum Press, New York (1989) 231–235.

    Google Scholar 

  72. S. Alpert, D. Hanahan, and G. Teitelman, Hybrid insulin genes reveal a developmental lineage for pancreatic endocrine cells and imply a relationship with neurons, Cell 53:295–309 (1988).

    Article  PubMed  CAS  Google Scholar 

  73. F. Lauder and F. Bloom, Ontogeny of monamine neurons in the locus coeruleus, raphe nuclei and substantia nigra of the rat. I. Cell differentiation, J Comp Neurol 155: 469–482, (1974).

    Article  PubMed  CAS  Google Scholar 

  74. LA. Specht, V.M. Pickel, T.H. Joh, and D.J. Reis, Light microscopic immunocytochemical localization of tyrosine hydroxylase in prenatal rat brain. I. Early ontogeny, J Comp Neurol 199:233–253 (1981).

    Article  PubMed  CAS  Google Scholar 

  75. D.J. Drucker and S.L. Asa, Glucagon gene expression in vertebrate brain, J Biol Chem 263: 13475–13478 (1988).

    PubMed  CAS  Google Scholar 

  76. V.K.M. Han, M.A. Hynes, C. Jin, J.M. Towle, and P.K. Lund, Cellular localization of proglucagon/glucagon–like peptide I messenger RNAs in rat brain, J Neuroscience Res 16:97–(1986).

    Article  CAS  Google Scholar 

  77. M.T. Rojeski and J. Roth, Messenger RNA for insulin in brain and other extrapancreatic sites, Clin Res 38:296A (1990).

    Google Scholar 

  78. R. Schechter, C. Bogey, K. Jackson, and J. R. Gavin, III, Insulin support of neuron cell growth by endocrine and paracrine pathways, Ped Res 27:52A (1990).

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, St. Louis University School of Medicine, St. Louis, Mo., USA

    Sherin U. Devaskar

  2. The Pediatric Research Institute, Cardinal Glennon Children’s Hospital, St. Louis, Mo., USA

    Sherin U. Devaskar

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  1. Sherin U. Devaskar
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Editors and Affiliations

  1. University of Florida, Gainesville, Florida, USA

    Mohan K. Raizada

  2. National Institutes of Health, Bethesda, Maryland, USA

    Derek LeRoith

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© 1991 Plenum Press, New York

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Devaskar, S.U. (1991). A Review of Insulin/Insulin-Like Peptide in the Central Nervous System. In: Raizada, M.K., LeRoith, D. (eds) Molecular Biology and Physiology of Insulin and Insulin-Like Growth Factors. Advances in Experimental Medicine and Biology, vol 293. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5949-4_34

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  • DOI: https://doi.org/10.1007/978-1-4684-5949-4_34

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