Conversion of Adult Pancreatic α-cells to β-cells After Extreme β-cell Loss
| Autor: | Fabrizio Thorel, Simona Chera, Isabelle Avril, Virginie Nepote, Pedro Luis Herrera, Renaud Desgraz, Kenji Kohno |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Adult
medicine.medical_specialty Cell signaling insulin transdifferentiation Cellular differentiation Cell α β Heterologous Biology precursor cell Article Internal medicine Insulin-Secreting Cells medicine diphtheria toxin Humans pancreas mouse gamma-Aminobutyric Acid transgenic Multidisciplinary cell plasticity islet diabetes Cell growth Regeneration (biology) reprogramming Cell cycle cell ablation Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 1 glucagon regeneration cell lineage tracing Developmental biology Signal Transduction |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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