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

Nature. 2010 Apr 22;464(7292):1149-54. doi: 10.1038/nature08894. Epub 2010 Apr 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Count
  • Cell Death / drug effects
  • Cell Differentiation / physiology*
  • Cell Lineage
  • Cell Proliferation
  • Cell Transdifferentiation / physiology*
  • Cellular Reprogramming
  • Diphtheria Toxin / pharmacology
  • Diphtheria Toxin / toxicity
  • Female
  • Glucagon / biosynthesis
  • Glucagon / genetics
  • Glucagon / metabolism
  • Glucagon-Secreting Cells / cytology*
  • Glucagon-Secreting Cells / metabolism
  • Humans
  • Insulin / biosynthesis
  • Insulin / metabolism
  • Insulin / pharmacology
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Male
  • Mice
  • Mice, Transgenic
  • Rats
  • Regeneration / physiology


  • Biomarkers
  • Diphtheria Toxin
  • Insulin
  • Glucagon