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Nature. 2010 Apr 22;464(7292):1149-54. doi: 10.1038/nature08894. Epub 2010 Apr 4.

Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss.

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  • 1Department of Cell Physiology & Metabolism, University of Geneva Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.

Abstract

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

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PMID:
20364121
[PubMed - indexed for MEDLINE]
PMCID:
PMC2877635
Free PMC Article

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