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

Fabrizio Thorel, Virginie Népote, Isabelle Avril, Kenji Kohno, Renaud Desgraz, Simona Chera and Pedro L. Herrera ()
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Fabrizio Thorel: University of Geneva Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland
Virginie Népote: University of Geneva Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland
Isabelle Avril: University of Geneva Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland
Kenji Kohno: Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), 8916-5 Takayama, Ikoma, Nara 630-0192, Japan
Renaud Desgraz: University of Geneva Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland
Simona Chera: University of Geneva Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland
Pedro L. Herrera: University of Geneva Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland

Nature, 2010, vol. 464, issue 7292, 1149-1154

Abstract: Abstract 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.

Date: 2010
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DOI: 10.1038/nature08894

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