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Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus

Nature volume 373, pages 448–451 (1995)Cite this article

Abstract

MOST patients with non-insulin-dependent diabetes mellitus are resistant to both endogenous and exogenous insulin1. Insulin resistance precedes the onset of this disease2 –4, suggesting that it may be an initial abnormality. Insulin-receptor kinase activity is impaired in muscle, fibroblasts and other tissues of many patients with non-insulin-dependent diabetes mellitus5, but abnormalities in the insulin-receptor gene do not appear to be the cause of this decreased kinase activity6, 7. Skin fibroblasts from certain insulin-resistant patients contain an inhibitor of insulin-receptor tyrosine kinase8, 9. Here we show that this inhibitor is a membrane glycoprotein, termed PC-1 (refs 10,11). We find that PC-1 activity is increased in fibroblasts from seven of nine patients with typical non-insulin-dependent diabetes mellitus. In addition, overexpression of PC-1 in transfected cultured cells reduces insulin-stimulated tyrosine kinase activity. These studies raise the possibility that PC-1 has a role in the insulin resistance of non-insulin-dependent diabetes mellitus.

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References

  1. Reaven, G. M. Diabetes 35, 1595–1607 (1988).

    Article  Google Scholar 

  2. Bogardus, C. et al. Diabetes 38, 1423–1432 (1989).

    Article  CAS  Google Scholar 

  3. Warram, J. H. et al. A. Intern. Med. 113, 909–915 (1990).

    Article  CAS  Google Scholar 

  4. Martin, B. C. et al. Lancet 340, 925–929 (1992).

    Article  CAS  Google Scholar 

  5. Haring, H. & Obermaier-Kusser, B. Diabetes Metab. Rev. 5, 431–441 (1989).

    Article  CAS  Google Scholar 

  6. Taylor, S. I. Diabetes 41, 1473–1490 (1992).

    Article  CAS  Google Scholar 

  7. Moller, D. E. & Flier, J. S. New Engl. J. Med. 325, 938–948 (1991).

    Article  CAS  Google Scholar 

  8. Sbraccia, P. et al. Diabetes 40, 295–299 (1991).

    Article  CAS  Google Scholar 

  9. Maddux, B. A., Sbraccia, P., Reaven, G. M., Moller, D. E. & Goldfine, I. D. J. Clin. Endocr. Metab. 77, 73–79 (1993).

    CAS  PubMed  Google Scholar 

  10. Buckley, M. F., Loveland, K. A., McKinstry, W. J., Garson, O. M. & Goding, J. W. J. biol, Chem. 265, 29, 17506–17511 (1990).

    CAS  Google Scholar 

  11. Funakoshi, I. et al. Archs Biochem. Biophys. 295, 180–187 (1992).

    Article  CAS  Google Scholar 

  12. Yoshida, H., Fukui, S., Funakoshi, I. & Yamashina, I. J. Biochem. 93, 1641–1648 (1983).

    Article  CAS  Google Scholar 

  13. Greene, S. F., Johnson, P. R., Eiffert, K. C., Greenwood, M. R. C. & Stern, J. S. Obesity Res. 2, 432–443 (1994).

    Article  CAS  Google Scholar 

  14. Milazzo, G. et al. Cancer Res. 52, 3924–3930 (1992).

    CAS  PubMed  Google Scholar 

  15. Myers, M. G. & White, M. F. Diabetes 42, 643–650 (1993).

    Article  CAS  Google Scholar 

  16. Rebbe, N. F., Tong, B. D. & Hickman, S. Molec. Immun. 30, 87–93 (1993).

    Article  CAS  Google Scholar 

  17. Oda, Y., Kuo, M-D., Huang, S. S. & Huang, J. S. J. biol. Chem. 266, 16791–16795 (1991).

    CAS  PubMed  Google Scholar 

  18. Huang, R. et al. J. clin. Invest. 94, 560–567 (1994).

    Article  CAS  Google Scholar 

  19. Forsayeth, J., Maddux, B. & Goldfine, I. D. Diabetes 35, 837–846 (1986).

    Article  CAS  Google Scholar 

  20. Hartmann, K. K. P. et al. Endocrinology 127, 2038–2040 (1990).

    Article  CAS  Google Scholar 

  21. Suva, L. J. et al. Gene 77, 95–105 (1989).

    Article  CAS  Google Scholar 

Download references

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Authors and Affiliations

  1. Division of Diabetes and Endocrine Research, Mount Zion Medical Center of the University of California, San Francisco, San Francisco, California, 94115, USA

    Betty A. Maddux, Paolo Sbraccia, Shinobu Kumakura, Shlomo Sasson, Jack Youngren, Alexander Fisher & Ira D. Goldfine

  2. Genentech Inc., South San Francisco, California, 94080, USA

    Steven Spencer, Andrew Grupe, William Henzel & Timothy A. Stewart

  3. Stanford University, VA Medical Center, Palo Alto, California, 94304, USA

    Gerald M. Reaven

Authors
  1. Betty A. Maddux
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  2. Paolo Sbraccia
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  3. Shinobu Kumakura
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  4. Shlomo Sasson
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  5. Jack Youngren
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  6. Alexander Fisher
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  7. Steven Spencer
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  8. Andrew Grupe
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  9. William Henzel
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  10. Timothy A. Stewart
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  11. Gerald M. Reaven
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  12. Ira D. Goldfine
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Maddux, B., Sbraccia, P., Kumakura, S. et al. Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus. Nature 373, 448–451 (1995). https://doi.org/10.1038/373448a0

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