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Promises and pitfalls of beta cell–replacement therapies

Diabetes therapeutic approaches continue to expand and to be refined. As the field moves toward more intensive insulin- and cell-based therapies, care must be taken to mimic healthy physiological insulin dynamics and avoid hyperinsulinemia, with its deleterious downstream complications.

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Fig. 1: Progress and future challenges in the development of stem cell–derived beta-like cells for the treatment of diabetes and prevention of long-term complications.

References

  1. 1.

    Gregory, J. M., Cherrington, A. D. & Moore, D. J. Diabetes 69, 837–847 (2020).

    CAS  Article  Google Scholar 

  2. 2.

    Heller, S. Diabetes Res. Clin. Pract. 65 (Suppl. 1), S23–S27 (2004).

  3. 3.

    Warnock, G. L. et al. Transplantation 86, 1762–1766 (2008).

    Article  Google Scholar 

  4. 4.

    Gamble, A., Pepper, A. R., Bruni, A. & Shapiro, A. M. J. Islets 10, 80–94 (2018).

    Article  Google Scholar 

  5. 5.

    Kolic, J. et al. Endocrinology 161, bqaa162 (2020).

    Article  Google Scholar 

  6. 6.

    Pagliuca, F. W. et al. Cell 159, 428–439 (2014).

    CAS  Article  Google Scholar 

  7. 7.

    Rezania, A. et al. Nat. Biotechnol. 32, 1121–1133 (2014).

    CAS  Article  Google Scholar 

  8. 8.

    Mahaddalkar, P. U. et al. Nat. Biotechnol. 38, 1061–1072 (2020).

    CAS  Article  Google Scholar 

  9. 9.

    Velazco-Cruz, L. et al. Stem Cell Rep. 12, 351–365 (2019).

    CAS  Article  Google Scholar 

  10. 10.

    Marchetti, P. et al. Diabetes 43, 827–830 (1994).

    CAS  Article  Google Scholar 

  11. 11.

    Seino, S., Shibasaki, T. & Minami, K. J. Clin. Invest. 121, 2118–2125 (2011).

    CAS  Article  Google Scholar 

  12. 12.

    Satin, L. S., Butler, P. C., Ha, J. & Sherman, A. S. Mol. Aspects Med. 42, 61–77 (2015).

    CAS  Article  Google Scholar 

  13. 13.

    Lin, J. M., Fabregat, M. E., Gomis, R. & Bergsten, P. Diabetes 51, 988–993 (2002).

    CAS  Article  Google Scholar 

  14. 14.

    Wortham, M. et al. Preprint at bioRxiv https://doi.org/10.1101/742403 (2019).

  15. 15.

    Zhang, A. M. Y., Wellberg, E. A., Kopp, J. L. & Johnson, J. D. Diabetes Metab. J. 45, 285–311 (2021).

    Article  Google Scholar 

Download references

Acknowledgements

We thank many colleagues, including J. Kushner, F. Lynn and T. Kieffer, for illuminating discussions on this topic over the years. We thank all of the authors whose work has inspired us.

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J.K. and J.D.J. cowrote the manuscript.

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Correspondence to James D. Johnson.

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Peer review information Nature Metabolism thanks the anonymous reviewers for their contribution to the peer review of this work.

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Kolic, J., Johnson, J.D. Promises and pitfalls of beta cell–replacement therapies. Nat Metab 3, 1036–1037 (2021). https://doi.org/10.1038/s42255-021-00433-4

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