Conversion of adult pancreatic α-cells to β-cells after extreme β-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...

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) 2010-04, Vol.464 (7292), p.1149-1154
Main Authors: THOREL, Fabrizio, NEPOTE, Virginie, AVRIL, Isabelle, KOHNO, Kenji, DESGRAZ, Renaud, CHERA, Simona, HERRERA, Pedro L
Format: Article
Language:English
Subjects:
Ablation
Adults
Animals
Biological and medical sciences
Biomarkers - metabolism
Care and treatment
Cell Count
Cell Death - drug effects
Cell differentiation
Cell Differentiation - physiology
Cell Lineage
Cell Proliferation
Cell Transdifferentiation - physiology
Cellular Reprogramming
Conversion
Demand
Development and progression
Diabetes
Diabetes. Impaired glucose tolerance
Differentiation
Diphtheria Toxin - pharmacology
Diphtheria Toxin - toxicity
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Female
Gene therapy
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
Islands of Langerhans
Male
Medical sciences
Methods
Mice
Mice, Transgenic
Observations
Properties
Rats
Regeneration
Regeneration (Biology)
Regeneration - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature08894