Nature 464, 1149-1154 (22 April 2010) | doi:10.1038/nature08894; Received 8 May 2009; Accepted 10 February 2010; Published online 4 April 2010

Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss

Fabrizio Thorel1,3, Virginie Népote1,3, Isabelle Avril1,3, Kenji Kohno2, Renaud Desgraz1, Simona Chera1 & Pedro L. Herrera1

  1. Department of Cell Physiology & Metabolism, University of Geneva Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland
  2. Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), 8916-5 Takayama, Ikoma, Nara 630-0192, Japan
  3. These authors contributed equally to this work.

Correspondence to: Pedro L. Herrera1 Correspondence and requests for materials should be addressed to P.L.H. (Email:


Pancreatic insulin-producing β-cells have a long lifespan, such that in healthy conditions they replicate little during a lifetime. Nevertheless, they show increased self-duplication after increased metabolic demand or after injury (that is, β-cell loss). It is not known whether adult mammals can differentiate (regenerate) new β-cells after extreme, total β-cell loss, as in diabetes. This would indicate differentiation from precursors or another heterologous (non-β-cell) source. Here we show β-cell regeneration in a transgenic model of diphtheria-toxin-induced acute selective near-total β-cell ablation. If given insulin, the mice survived and showed β-cell mass augmentation with time. Lineage-tracing to label the glucagon-producing α-cells before β-cell ablation tracked large fractions of regenerated β-cells as deriving from α-cells, revealing a previously disregarded degree of pancreatic cell plasticity. Such inter-endocrine spontaneous adult cell conversion could be harnessed towards methods of producing β-cells for diabetes therapies, either in differentiation settings in vitro or in induced regeneration.


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