More is better: combinatorial therapy to restore β-cell function in diabetes

Current pharmacological options for diabetes treatment help patients control blood glucose levels but do not reverse the decline in insulin-secreting β-cells. A new study now shows that a pharmacological combination of insulin and a GLP-1–oestrogen conjugate not only decreases daily insulin requirements but also improves β-cell function.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Summary of the steps during loss of β-cell identity, analysed by single-cell RNA-sequencing.


  1. 1.

    Weir, G. C. & Bonner-Weir, S. Diabetes 53(Suppl. 3), S16–S21 (2004).

    CAS  Article  Google Scholar 

  2. 2.

    Banting, F. G. & Best, C. H. J. Lab. Clin. Med. 7, 251–266 (1922).

    CAS  Google Scholar 

  3. 3.

    De Jesus, D. F. & Kulkarni, R. N. Mol. Metab. 27S, S42–S48 (2019).

    Article  Google Scholar 

  4. 4.

    Talchai, C., Xuan, S., Lin, H. V., Sussel, L. & Accili, D. Cell 150, 1223–1234 (2012).

    CAS  Article  Google Scholar 

  5. 5.

    Rui, J. et al. Cell Metab. 25, 727–738 (2017).

    CAS  Article  Google Scholar 

  6. 6.

    Dirice, E. et al. Nat. Metab. 1, 509–518 (2019).

    Article  Google Scholar 

  7. 7.

    Sachs, S. Nat. Metab. https://doi.org/10.1038/s42255-020-0171-3 (2020).

    Article  Google Scholar 

  8. 8.

    Like, A. A. & Rossini, A. A. Science 193, 415–417 (1976).

    CAS  Article  Google Scholar 

  9. 9.

    Kulkarni, R. N. et al. Cell 96, 329–339 (1999).

    CAS  Article  Google Scholar 

  10. 10.

    Le May, C. et al. Proc. Natl Acad. Sci. USA 103, 9232–9237 (2006).

    Article  Google Scholar 

  11. 11.

    Drucker, D. J., Philippe, J., Mojsov, S., Chick, W. L. & Habener, J. F. Proc. Natl Acad. Sci. USA 84, 3434–3438 (1987).

    CAS  Article  Google Scholar 

  12. 12.

    Finan, B. et al. Nat. Med. 18, 1847–1856 (2012).

    CAS  Article  Google Scholar 

  13. 13.

    Bader, E. et al. Nature 535, 430–434 (2016).

    CAS  Article  Google Scholar 

  14. 14.

    Karakose, E., Ackeifi, C., Wang, P. & Stewart, A. F. Diabetologia 61, 1693–1699 (2018).

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Rohit N. Kulkarni.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

De Jesus, D.F., Kulkarni, R.N. More is better: combinatorial therapy to restore β-cell function in diabetes. Nat Metab 2, 130–131 (2020). https://doi.org/10.1038/s42255-020-0176-y

Download citation


Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing