Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss.
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.
Thorel
Fabrizio
F
Department of Cell Physiology & Metabolism, University of Geneva Faculty of Medicine, 1 rue Michel-Servet, CH-1211 Geneva 4, Switzerland.
Népote
Virginie
V
Avril
Isabelle
I
Kohno
Kenji
K
Desgraz
Renaud
R
Chera
Simona
S
Herrera
Pedro L
PL
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000502:physiology*; D019070:Cell Lineage; D049109:Cell Proliferation; D054338:Cell Transdifferentiation / Q000502:physiology*; D065150:Cellular Reprogramming; D004167:Diphtheria Toxin / Q000494:pharmacology / Q000633:toxicity; D005260:Female; D005934:Glucagon / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D012038:Regeneration / Q000502:physiology
D015415:Biomarkers; D004167:Diphtheria Toxin; D007328:Insulin; D005934:Glucagon