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Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro

Nature volume 335, pages 632–635 (1988)Cite this article

Abstract

Insulin resistance occurs in a variety of conditions, including diabetes, obesity and essential hypertension1, but its underlying molecular mechanisms are unclear. In type 2 (non-insulin-dependent) diabetes mellitus, it is insulin-resistance in skeletal muscle, the chief site of insulin-mediated glucose disposal in humans2, that predominantly accounts for the low rates of glucose clearance from the blood, and hence for impaired glucose tolerance3. Human type 2 diabetes is characterized by a decrease in non-oxidative glucose storage (muscle glycogen synthesis)4,5, and by the deposition of amyloid in the islets of Langerhans6,7. Amylin is a 37-amino-acid peptide which is a major component of islet amyloid and has structural similarity to human calcitonin gene-related peptide-2 (CGRP-2; ref.8). CGRP is a neuropeptide which may be involved in motor activity in skeletal muscle9,10. We now report that human pancreatic amylin and rat CGRP-1 are potent inhibitors of both basal and insulin-stimulated rates of glycogen synthesis in stripped rat soleus muscle in vitro. These results may provide a basis for a new understanding of the molecular mechanisms that cause insulin resistance in skeletal muscle.

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References

  1. Ferrannini, E. et al. New Engl. J. Med. 317, 350–357 (1987).

    Article  CAS  Google Scholar 

  2. DeFronzo, R. A. & Ferrannini, E. Diabetes/ Metabolism Rev. 3, 415–459 (1987).

    Article  CAS  Google Scholar 

  3. Kolterman, O. G. Diabetes/ Metabolism Rev. 3, 399–414 (1987).

    Article  CAS  Google Scholar 

  4. Bogardus, C., Lillioja, S., Stone, K. & Mott, D. J. clin. Invest. 73, 1185–1190 (1984).

    Article  CAS  Google Scholar 

  5. Meyer, H. U., Curchod, B., Maeder, E., Pahud, P. & Jequier, E. Diabetes 29, 752–756 (1980).

    Article  CAS  Google Scholar 

  6. Opie, E. L. J. exp. Med. 5, 397–428 (1900).

    Article  Google Scholar 

  7. Bell, E. T. Diabetes 1, 341–344 (1952).

    Article  CAS  Google Scholar 

  8. Cooper, G.J.S. et al. Proc. natn. Acad. Sci. U.S.A. 84, 8628–8632 (1987).

    Article  ADS  CAS  Google Scholar 

  9. Mason, R. T. et al. Nature 308, 653–655 (1984).

    Article  ADS  CAS  Google Scholar 

  10. Takami, K. et al. Neurosci. Lett. 60, 227–230 (1985).

    Article  CAS  Google Scholar 

  11. Rennie, M. J. & Edwards, R. H. T. Carbohydrate Metabolism and its Disorders Vol. 3. (eds Randle, P. J., Steiner, D. F. & Whelan, W. J.) 1–121 (Academic, London, 1981).

    Google Scholar 

  12. Foulkes, J. G., Gehen, P., Strada, S. J., Everson, W. J. & Jefferson, L. S. J. biol. Chem. 257, 12493–12496 (1982).

    CAS  PubMed  Google Scholar 

  13. Challiss, R. A. J., Leighton, B., Lozeman, F. J. & Newsholme, E. A. in Topics and Perspectives in Adenosine Research (eds Gerlach, E. & Becker, B. F.) 275–285 (Springer, Berlin, 1987).

    Book  Google Scholar 

  14. Foord, S. M. & Craig, R. K. Biochem. Soc. Trans. 15, 714–716 (1987).

    Article  CAS  Google Scholar 

  15. Tschoop, F. A. et al. Proc. natn. Acad. Sci. U.S.A. 82, 248–252 (1985).

    Article  ADS  Google Scholar 

  16. Seifert, H. et al. Am. J. Physiol. 249, G147–G151 (1985).

    CAS  PubMed  Google Scholar 

  17. Leighton, B., Kowalchuk, J. M., Challiss, R. A. J. & Newsholme, E. A. Am. J. Physiol. 255, E41–E45 (1988).

    CAS  PubMed  Google Scholar 

  18. Wajngot, A., Roovete, A., Vranic, M., Luft, R. & Efendic, S. Proc. natn. Acad. Sci. U.S.A. 79, 4432–4436 (1982).

    Article  ADS  CAS  Google Scholar 

  19. Yki-Jarvinen, H., Mott, D., Young, A. A., Stone, K. & Bogardus, C. J. clin. Invest. 80, 95–100 (1987).

    Article  CAS  Google Scholar 

  20. Young, A. A., Bogardus, C., Wolfe-Lopez, D. & Mott, D. M. Diabetes 37, 303–308 (1988).

    Article  CAS  Google Scholar 

  21. Hewick, R. M., Hunkapiller, M. W., Hood, L. E. & Dreyer, W. J. J. bio. chem. 256, 7990–7997 (1981).

    CAS  Google Scholar 

  22. Heinrikson, R. L. & Meredith, S. C. Analyt. Biochem. 136, 65–74 (1984).

    Article  CAS  Google Scholar 

  23. Ishizuka, J., Greely, G. H., Cooper, C. W. & Thompson, J. C., Regul. Peptides 20, 73–82 (1988).

    Article  CAS  Google Scholar 

  24. Leighton, B., Challiss, R. A. J., Lozeman, F. J. & Newsholme, E. A. Biochem. J. 20, 551–554 (1988).

    Google Scholar 

  25. Leighton, B. et al. Int. J. Biochem. 20, 23–27 (1988).

    Article  CAS  Google Scholar 

  26. James, D. E., Jenkins, A. B. & Kraegen, E. W. Am. J. Physiol. 248, E567–E574 (1985).

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

    Brendan Leighton

  2. Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

    Garth J. S. Cooper

Authors
  1. Brendan Leighton
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  2. Garth J. S. Cooper
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Leighton, B., Cooper, G. Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro. Nature 335, 632–635 (1988). https://doi.org/10.1038/335632a0

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