Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss
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.
From the paper
- Animals
During the initial 5 months, animals were regularly given subcutaneous insulin implants whenever their glycemia was above 20mM (16 mice were studied in total).
- Events by group
… had dropped to 0.3% and 0.01% of the control value, respectively. β-cell loss was confirmed histologically: the β-cell mass decreased from 1,594μg to 6μg 15 days post-DT, which corresponds to a disappearance of 99.6% of the β-cells.
Quoted word for word from the full text on PubMed Central.
The paper
University of Geneva
Nature, 4 Apr 2010, Open access, accepted manuscript
