Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss
Fabrizio Thorel,Virginie Nepote,Isabelle Avril,Kenji Kohno,Renaud Desgraz,Simona Chera,Pedro Luis Herrera +6 more
TLDR
In this article, a transgenic model of diphtheria-toxin-induced acute selective near-total beta-cell ablation was used to investigate whether adult mammals can differentiate (regenerate) new beta-cells after extreme, total β-cell loss, as in diabetes.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.read more
Citations
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Mesenchymal Stem Cells Ameliorate Hyperglycemia in Type I Diabetic Developing Male Rats
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TL;DR: The published results of beta-cell regeneration are discussed and the advantages and disadvantages illustrated by these experiments are discussed, which have set trends for regeneration medicine, directed at minimizing genome modifications and invasive procedures.
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R-spondin1 deficiency enhances β-Cell neogenesis in a murine model of diabetes.
TL;DR: Findings indicate that Rspo1 is a negative regulator of andbgr;-cell neogenesis, development, and survival in the face of STZ-induced diabetes, providing a therapeutic target for the enhancement of &bgr ;-cell mass.
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