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Glucagon receptor antagonists might stimulate β-cell expansion

In a recent issue of Cell Reports, Xi et al. reported on their studies of an anti-glucagon receptor antibody in several mouse models of insulin-deficient diabetes mellitus, in which they show substantial increase in β-cell mass from enhanced replication and transdifferentiation of glucagon-expressing α-cells to insulin-expressing β-cells.

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Fig. 1: Glucagon receptor antagonists can lead to regeneration of β-cells in insulin-deficient mice, but their effect in humans is unclear.


  1. Xi, Y. et al. Glucagon-receptor-antagonism-mediated β-cell regeneration as an effective anti-diabetic therapy. Cell Rep. 39, 110872 (2022).

    Article  CAS  Google Scholar 

  2. Lee, Y. H., Wang, M. Y., Yu, X. X. & Unger, R. H. Glucagon is the key factor in the development of diabetes. Diabetologia 59, 1372–1375 (2016).

    Article  CAS  Google Scholar 

  3. Wang, M. Y. et al. Glucagon receptor antibody completely suppresses type 1 diabetes phenotype without insulin by disrupting a novel diabetogenic pathway. Proc. Natl Acad. Sci. USA 112, 2503–2508 (2015).

    Article  CAS  Google Scholar 

  4. Gelling, R. W. et al. Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice. Proc. Natl Acad. Sci. USA 100, 1438–1443 (2003).

    Article  CAS  Google Scholar 

  5. Wang, M. Y. et al. Glucagon blockade restores functional β-cell mass in type 1 diabetic mice and enhances function of human islets. Proc. Natl Acad. Sci. USA 118, e2022142118 (2021).

    Article  CAS  Google Scholar 

  6. Okamoto, H. et al. Glucagon receptor inhibition normalizes blood glucose in severe insulin-resistant mice. Proc. Natl Acad. Sci. USA 114, 2753–2758 (2017).

    Article  CAS  Google Scholar 

  7. Thorel, F. et al. Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss. Nature 464, 1149–1154 (2010).

    Article  CAS  Google Scholar 

  8. Nir, T., Melton, D. A. & Dor, Y. Recovery from diabetes in mice by beta cell regeneration. J. Clin. Invest. 117, 2553–2561 (2007).

    Article  CAS  Google Scholar 

  9. Okamoto, H. et al. Glucagon receptor blockade with a human antibody normalizes blood glucose in diabetic mice and monkeys. Endocrinology 156, 2781–2794 (2015).

    Article  CAS  Google Scholar 

  10. Scheen, A. J., Paquot, N. & Lefèbvre, P. J. Investigational glucagon receptor antagonists in phase I and II clinical trials for diabetes. Expert Opin. Investig. Drugs 26, 1373–1389 (2017).

    Article  CAS  Google Scholar 

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Correspondence to Susan Bonner-Weir.

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Rubin de Celis, M.F., Bonner-Weir, S. Glucagon receptor antagonists might stimulate β-cell expansion. Nat Rev Endocrinol 18, 659–660 (2022).

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