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

Article

关键词: DIPHTHERIA-TOXIN RECEPTOR;    TRANSCRIPTION FACTOR;    MOUSE PANCREAS;    IN-VITRO;    ECTOPIC EXPRESSION;    GLUCAGON-SECRETION;    ENDOCRINE PANCREAS;    DIABETES-MELLITUS;    PROGENITOR CELLS;    REGENERATION;   

DOI  :  10.1038/nature08894

来源: SCIE

【 摘 要 】

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 transgenicmodel 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.

【 授权许可】

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