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Diacylglycerol-mediated insulin resistance

Nature Medicine volume 16, pages 400402 (2010) | Download Citation

Abstract

Understanding the molecular mechanisms of insulin resistance remains a major medical challenge of the twenty-first century. Over the last half-century, many hypotheses have been proposed to explain insulin resistance, and, most recently, inflammation associated with alterations in adipocytokines has become the prevailing hypothesis. Here we discuss diacylglycerol-mediated insulin resistance as an alternative and unifying hypothesis to explain the most common forms of insulin resistance associated with obesity and type 2 diabetes mellitus, as well as lipodystrophy and aging.

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References

  1. 1.

    International Diabetes Federation. (2009).

  2. 2.

    et al. N. Engl. J. Med. 322, 223–228 (1990).

  3. 3.

    et al. N. Engl. J. Med. 341, 240–246 (1999).

  4. 4.

    , & J. Clin. Invest. 89, 1069–1075 (1992).

  5. 5.

    , , , & J. Clin. Invest. 90, 1323–1327 (1992).

  6. 6.

    et al. Diabetes 49, 701–707 (2000).

  7. 7.

    et al. J. Clin. Invest. 98, 378–385 (1996).

  8. 8.

    & J. Clin. Invest. 39, 1157–1175 (1960).

  9. 9.

    , & J. Clin. Invest. 118, 2992–3002 (2008).

  10. 10.

    , & J. Clin. Invest. 116, 1793–1801 (2006).

  11. 11.

    Nature 444, 860–867 (2006).

  12. 12.

    Int. J. Obes. (Lond.) 32 Suppl 7, S52–S54 (2008).

  13. 13.

    , , & Endocr. Rev. 23, 599–622 (2002).

  14. 14.

    et al. Cell 96, 329–339 (1999).

  15. 15.

    et al. Cell 88, 561–572 (1997).

  16. 16.

    , , & Lancet 1, 785–789 (1963).

  17. 17.

    , & Biochem. J. 93, 652–665 (1964).

  18. 18.

    , , & Ann. NY Acad. Sci. 131, 324–333 (1965).

  19. 19.

    et al. J. Clin. Invest. 97, 2859–2865 (1996).

  20. 20.

    et al. J. Clin. Invest. 103, 253–259 (1999).

  21. 21.

    et al. J. Biol. Chem. 277, 50230–50236 (2002).

  22. 22.

    et al. Diabetes 48, 1270–1274 (1999).

  23. 23.

    , , & Diabetes 51, 2005–2011 (2002).

  24. 24.

    et al. Proc. Natl. Acad. Sci. USA 98, 7522–7527 (2001).

  25. 25.

    et al. J. Clin. Invest. 113, 756–763 (2004).

  26. 26.

    et al. J. Clin. Invest. 117, 1679–1689 (2007).

  27. 27.

    et al. J. Clin. Invest. 117, 1995–2003 (2007).

  28. 28.

    et al. Proc. Natl. Acad. Sci. USA 104, 16480–16485 (2007).

  29. 29.

    et al. J. Clin. Invest. 114, 823–827 (2004).

  30. 30.

    et al. Cell Metab. 11, 70–76 (2010).

  31. 31.

    et al. J. Biol. Chem. 279, 32345–32353 (2004).

  32. 32.

    et al. J. Clin. Invest. 117, 739–745 (2007).

  33. 33.

    et al. Cell Metab. 9, 252–264 (2009).

  34. 34.

    et al. Cell Metab. 2, 55–65 (2005).

  35. 35.

    et al. J. Biol. Chem. 282, 22678–22688 (2007).

  36. 36.

    et al. J. Clin. Invest. 116, 817–824 (2006).

  37. 37.

    et al. Proc. Natl. Acad. Sci. USA 104, 17075–17080 (2007).

  38. 38.

    et al. Lancet 362, 951–957 (2003).

  39. 39.

    et al. J. Clin. Invest. 109, 1345–1350 (2002).

  40. 40.

    et al. Am. J. Physiol. Endocrinol. Metab. 284, E274–E280 (2003).

  41. 41.

    et al. J. Clin. Invest. 115, 3587–3593 (2005).

  42. 42.

    et al. Diabetes 56, 1376–1381 (2007).

  43. 43.

    et al. Science 300, 1140–1142 (2003).

  44. 44.

    et al. Cell 132, 375–386 (2008).

  45. 45.

    et al. N. Engl. J. Med. 362, 1082–1089 (2009).

  46. 46.

    et al. J. Clin. Invest. 112, 1796–1808 (2003).

  47. 47.

    et al. J. Clin. Invest. 112, 1821–1830 (2003).

  48. 48.

    Science 325, 256–260 (2009).

  49. 49.

    , , , & N. Engl. J. Med. 350, 664–671 (2004).

  50. 50.

    , , , & J. Biol. Chem. 275, 8456–8460 (2000).

  51. 51.

    et al. Diabetes 54, 603–608 (2005).

  52. 52.

    & J. Appl. Physiol. 102, 814–816 (2007).

  53. 53.

    J. Appl. Physiol. 102, 820 (2007).

  54. 54.

    , , , & Diabetes 45, 881–885 (1996).

  55. 55.

    et al. Diabetes 51, 797–802 (2002).

  56. 56.

    et al. N. Engl. J. Med. 355, 2297–2307 (2006).

  57. 57.

    et al. Diabetes 56, 1034–1041 (2007).

  58. 58.

    et al. Diabetes 52, 1311–1318 (2003).

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Author information

Affiliations

  1. Derek M. Erion and Gerald I. Shulman are at the Howard Hughes Medical Institute, Departments of Internal Medicine and Cellular & Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USA.

    • Derek M Erion
    •  & Gerald I Shulman

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Gerald I Shulman.

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DOI

https://doi.org/10.1038/nm0410-400

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