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Effects of age on elements of insulin-signaling pathway in central nervous system of rats

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Abstract

Insulin resistance is known to play a pivotal role in type 2 diabetes. Senile individuals, besides being prone to insulin resistance and, consequently, to type 2 diabetes, manifest diseases of the central nervous system (CNS) that may be influenced by disturbances of insulin signaling in the brain, such as memory impairment, Parkinson disease, and Alzheimer disease. We investigated the expression and response to insulin of elements involved in the insulin-signaling pathway in the forebrain cortex and cerebellum of rats ages 1 d to 60 wk. The protein content of insulin receptors and SRC homology adaptor protein (SHC) did not change significantly along the time frame analyzed. However, insulin-induced tyrosine phosphorylation of the insulin receptor and SHC, and the association of SHC/growth factor receptor binding protein-2 (GRB2) decreased significantly from d 1 to wk 60 of life in both types of tissues. Moreover, the expression of SH protein tyrosine phosphatase-2 (SHP2), a tyrosine phosphatase involved in insulin signal transduction and regulation of the insulin signal, decreased significantly with age progression, in both the forebrain cortex and the cerebellum of rats. Thus, elements involved in the insulinsignaling pathway are regulated at the expression and/or functional level in the CNS, and this regulation may play a role in insulin resistance in the brain.

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References

  1. Schwartz, M. W., Figlewicz, D. P., Baskin, D. G., Woods, S. C., and Porte, D. jr. (1992). Endocr. Rev. 13, 387–414.

    Article  PubMed  CAS  Google Scholar 

  2. Baskin, D. G., Wilcox, B. J., Figlewicz, D. P., and Dorsa, D. M. (1988). TINS 11, 107–111.

    PubMed  CAS  Google Scholar 

  3. Hill, J. M., Lesniak, M. A., Pert, C. B., and Roth, J. (1986). Neuroscience 17, 1127–1138.

    Article  PubMed  CAS  Google Scholar 

  4. Moss, A. M., Unger, J. W., Moxley, R. T., and Levinngston, J. N. (1990). Proc. Natl. Acad. Sci. USA 87, 4453–4457.

    Article  PubMed  CAS  Google Scholar 

  5. Schwartz, M. W., Woods, S. C., Porte, D. Jr., Seeley, R. J., and Baskin, D. G. (2000). Nature 404, 661–671.

    PubMed  CAS  Google Scholar 

  6. Bondy, C. R. (1991). J. Neurosci. 11, 3442–3455.

    PubMed  CAS  Google Scholar 

  7. Garafolo, R. S. and Rosen, A. M. (1989). Mol. Cell. Biol. 9, 2806–2817.

    Google Scholar 

  8. Sherrard, R. M., Richardson, N. A., and Sara, V. R. (1997). Dev. Brain Res. 98, 102–113.

    Article  CAS  Google Scholar 

  9. Pomerange, M., Gavaret, J.-M., Jacquemin, C., Matricon, C., Toru-Delbauffe, D., and Pierre, M. (1988). Dev. Brain Res. 42, 77–83.

    Article  Google Scholar 

  10. Kappy, M. and Raizada, M. K. (1982). Brain Res. 249, 390–392.

    Article  PubMed  CAS  Google Scholar 

  11. Zaia, A. and Piantanelli, L. (2000). Mech. Ageing Dev. 113, 221–232.

    Article  Google Scholar 

  12. D’Costa, A. P., Xu, X., Ingram, R. L., and Sonntag, W. E. (1995). Neuroscience 65, 805–813.

    Article  PubMed  CAS  Google Scholar 

  13. Sonntag, W. E., Lynch, C. D., Bennett, S. A., Khan, A. S., Thornton, P. L., Cooney, P. T., Ingram, R. L., McShane, T., and Brunso-Bechtold, J. K. (1999). Neuroscience 88, 269–279.

    Article  PubMed  CAS  Google Scholar 

  14. Barnard, R. J., Lawani, L. O., Martin, D. A., Youngren, J. F., Sing, R., and Scheck, S. (1992). Am. Physiol. Soc. 25, E619-E626.

    Google Scholar 

  15. Goodman, N. M., Dluz, S. M., Mcelaney, M. A., Belur, E., and Ruderman, N. B. (1983). Am. J. Physiol. 244, E93-E100.

    PubMed  CAS  Google Scholar 

  16. Kono, S., Kuzuzya, H., Okamoto, M., Nishimura, H., Kosaki, A., Kakehi, T., Inove, G., Maeda, I., and Imura, H. (1990). Am. J. Physiol. 259, E27-E35.

    PubMed  CAS  Google Scholar 

  17. Yoshimasa, Y., Yamada, K., Ida, T., Kakehi, T., and Imura, H. (1988). Am. J. Physiol. 264, E319-E327.

    Google Scholar 

  18. Carvalho, C. R. O., Brenelli, S. L., Silva, A. C., Nunes, A. L. B., Velloso, L. A., and Saad, M. J. A. (1996). Endocrinology 137, 151–159.

    Article  PubMed  CAS  Google Scholar 

  19. Nadiv, O., Shinitzky, M., Manu, H., Hecht, D., Roberts, C. T. Jr., Le Roith, D., and Zick, Y. (1994). Biochem. J. 298, 443–450.

    PubMed  CAS  Google Scholar 

  20. Yamauchi, K., Milarski, K. L., Saltiel, A. R., and Pessin, J. E. (1995). Biochemistry 92, 664–668.

    CAS  Google Scholar 

  21. Baskin, D. G., Schwartz, M. W., Sipols, A. J., D’Alessio, D. A., Goldstein, B. J., and White, M. F. (1994). Endocrinology 134, 1952–1955.

    Article  PubMed  CAS  Google Scholar 

  22. Folli, F., Bonfanti, L., Renard, E., Kahn, C. R., and Merighi, A. (1994). J. Neurosci. 14, 6412–6422.

    PubMed  CAS  Google Scholar 

  23. de L. A. Fernandes, M. L. Saad, M. J., and Velloso, L. A. (1999). Brain Res. 826, 74–82.

    Article  Google Scholar 

  24. Herrera, R. and Rosen, O. M. (1986). J. Biol. Chem. 261, 11,980–11,985.

    CAS  Google Scholar 

  25. Perlman, R., Bottaro, D., White, M. F., and Kahn, C. R. (1989). J. Biol. Chem. 264, 8946–8950.

    PubMed  CAS  Google Scholar 

  26. White, M. F., Shoelson, S. E., Keutman, H., and Kahn, C. R. (1988). J. Biol. Chem. 263, 2969–2980.

    PubMed  CAS  Google Scholar 

  27. Virkamäki, A., Ueki, K., and Kahn, C. R. (1999). J. Clin. Invest. 103, 931–943.

    PubMed  Google Scholar 

  28. Páez-Espinosa, V., Carvalho, C. R. O., Alvarez-Rojas, F., Janeri, L., Velloso, L. A., Boschero, A. C., and Saad, M. J. A. (1998). Endocrine 8, 193–200.

    Article  PubMed  Google Scholar 

  29. Saad, M. J. A., Carvalho, C. R. O., Thirone, A. C. P., and Velloso, L. A. (1996). J. Biol. Chem. 271, 22,100–22,104.

    CAS  Google Scholar 

  30. Velloso, L. A., Folli, F., Sun, X. J., White, M. F., Saad, M. J. A., and Kahn, C. R. (1996). Proc. Natl. Acad. Sci. USA 93, 12,490–12,495.

    Article  CAS  Google Scholar 

  31. Obermeier, A., Lammers, T., Weismuller, K.-H., Jung, G., Schlessinger, J., and Ullrich, A. (1993). J. Biol. Chem. 268, 22,963–22,966.

    CAS  Google Scholar 

  32. Sasaoka, T., Rose, D., Jhun, B., Saltiel, A., Draznin, B., and Olefsky, J. (1994). J. Biol. Chem. 269, 13,689–13,694.

    CAS  Google Scholar 

  33. Segato, O., Pelicci, G., Giuli, S., Digiesi, P., Difiori, P. P., and Mcglade, J. (1993). Oncogene 8, 2105–2112.

    Google Scholar 

  34. Cattaneo, E. and Pellicci, P. G. (1998). TINS 21, 476–481.

    PubMed  CAS  Google Scholar 

  35. Giorgetti-Peraldi, S., Ottinger, E., Wolf, G., Ye, B., Burke, T. R. Jr., and Shoelson, S. E. (1997). Mol. Cell. Biol. 17, 1180–1188.

    PubMed  CAS  Google Scholar 

  36. Saad, M. J. A., Araki, E., Miralpeix, M., Rothenberg, P. L., White, M. F., and Kahn, C. R. (1992). J. Clin. Invest. 901, 839–1849.

    Google Scholar 

  37. Saad, M. J. A., Folli, F., Kahn, J., and Kahn, C. R. (1993). J. Clin. Invest. 92, 2065–2072.

    Article  PubMed  CAS  Google Scholar 

  38. Havrankova, J., Schemechel, D., Roth, J., and Brownstein, M. (1978). Proc. Natl. Acad. Sci. USA 75, 5737–5741.

    Article  PubMed  CAS  Google Scholar 

  39. Havrankova, J., Roth, J., and Browstein, M. (1978). Nature 272, 827–829.

    Article  PubMed  CAS  Google Scholar 

  40. Araki, T., Yamada, M., Osnishi, H., Sano, S.-I., Uetsuki, T., and Hatanaka, H. (2000). J. Neurochem. 74, 659–668.

    Article  PubMed  CAS  Google Scholar 

  41. Zaia, A. and Piantanelli, L. (1997). Mech. Ageing Dev. 98, 37–46.

    Article  PubMed  CAS  Google Scholar 

  42. Conti, L., De Fraja, C., Gulisano, M., Migliaccio, E., Govoni, S., and Cattaneo, E. (1997). Proc. Natl. Acad. Sci. USA 94, 8185–8190.

    Article  PubMed  CAS  Google Scholar 

  43. Bradford, M. M. (1976). Anal. Biochem. 72, 248–259.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, State University of Campinas, SP, Brazil

    Maria Luiza L. A. de Fernandes, Mário J. A. Saad &  Lício A. Velloso

  2. Pedro Ernesto University Hospital, Department of Internal Medicine, State University of Rio de Janeiro, RJ, Brazil

    Maria Luiza L. A. de Fernandes

Authors
  1. Maria Luiza L. A. de Fernandes
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  2. Mário J. A. Saad
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  3. Lício A. Velloso
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Correspondence to Lício A. Velloso.

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de Fernandes, M.L.L.A., Saad, M.J.A. & Velloso, L.A. Effects of age on elements of insulin-signaling pathway in central nervous system of rats. Endocr 16, 227–234 (2001). https://doi.org/10.1385/ENDO:16:3:227

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  • DOI: https://doi.org/10.1385/ENDO:16:3:227

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