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

Kohno, Kenji
Published in Nature. 2010, vol. 464, no. 7292, p. 1149-1154
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.
PMID: 20364121
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Research group Types cellulaires pancréatiques pendant l'ontogénèse (522)
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THOREL, Fabrizio et al. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. In: Nature, 2010, vol. 464, n° 7292, p. 1149-1154. doi: 10.1038/nature08894 https://archive-ouverte.unige.ch/unige:9054

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Deposited on : 2010-07-12

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