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Intolerable secretion and diabetes in tolerant transgenic mice, revisited

A new mouse model linking diabetes, insulin secretion and autoimmunity with a high-fat diet supports a shared mechanism for type 1 (T1D) and type 2 (T2D) diabetes. In this model, the protein secretion system of insulin-producing pancreatic beta cells is stressed, leading to increased beta cell apoptosis and diabetes via reduced levels of the transcription factor GLIS3, a pathogenic pathway that can be mimicked by a high-fat diet.

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Figure 1: Reduced GLIS3 function or a high-fat diet can compromise pancreatic islet beta cell mass and insulin secretion via ER stress, overload of the UPR and increased beta cell apoptosis to such an extent that diabetes develops.

References

  1. Parham, P. Nature 333, 500–503 (1988).

    Article  CAS  Google Scholar 

  2. Dooley, J. et al. Nat. Genet. 48, 519–527 (2016).

    Article  CAS  Google Scholar 

  3. Sun, J. et al. Mol. Aspects Med. 42, 105–118 (2015).

    Article  CAS  Google Scholar 

  4. Yamane, S. et al. J. Diabetes Investig. 2, 104–110 (2011).

    Article  CAS  Google Scholar 

  5. Støy, J. et al. Proc. Natl. Acad. Sci. USA 104, 15040–15044 (2007).

    Article  Google Scholar 

  6. Røder, M.E., Porte, D. Jr., Schwartz, R.S. & Kahn, S.E. J. Clin. Endocrinol. Metab. 83, 604–608 (1998).

    PubMed  Google Scholar 

  7. Truyen, I. et al. Diabetologia 48, 2322–2329 (2005).

    Article  CAS  Google Scholar 

  8. Lindahl, M. et al. Cell Rep. 7, 366–375 (2014).

    Article  CAS  Google Scholar 

  9. Senée, V. et al. Nat. Genet. 38, 682–687 (2006).

    Article  Google Scholar 

  10. Nogueira, T.C. et al. PLoS Genet. 9, e1003532 (2013).

    Article  CAS  Google Scholar 

  11. Hall, E. et al. BMC Med. 12, 103 (2014).

    Article  Google Scholar 

  12. Sone, H. & Kagawa, Y. Diabetologia 48, 58–67 (2005).

    Article  CAS  Google Scholar 

  13. Engin, F. J. Investig. Med. 64, 2–6 (2016).

    Article  Google Scholar 

  14. Cunha, D.A. et al. Diabetes 58, 2851–2862 (2009).

    Article  CAS  Google Scholar 

  15. Delong, T. et al. Science 351, 711–714 (2016).

    Article  CAS  Google Scholar 

Download references

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Correspondence to John A Todd.

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Todd, J. Intolerable secretion and diabetes in tolerant transgenic mice, revisited. Nat Genet 48, 476–477 (2016). https://doi.org/10.1038/ng.3560

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