Conversion of adult pancreatic α-cells to β-cells after extreme β-cell loss
Open accessAbstract
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.
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Emerging evidence in mice shows considerable plasticity within islets, allowing intraislet cell conversions, but only in the face of extreme β-cell destruction.
“Emerging evidence in mice also shows considerable plasticity within islets, allowing intraislet cell conversions, but only in the face of extreme β-cell destruction ( 38 ).”
From β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment (2014) · cites this paper as [38]
The Abstract reports α-to-β cell conversion in mice after near-total β-cell ablation. The Discussion says near-total loss *may* be needed to trigger this conversion, but notes that earlier, less severe injury models were not examined with lineage tracing. It therefore does not establish the claim’s categorical “only.” (LLM, conf=0.85)
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- Authors
- Thorel, F., Népote, V., Avril, I., Kohno, K., Desgraz, R., Chera, S., & Herrera, P. L.
- Affiliations
- University of Geneva (CH)
- Nara Institute of Science and Technology (JP)
- Corresponding author
- Herrera, Pedro L.
- Venue
- Nature
- Published
- 2010-04-04
- Volume
- 464
- Issue
- 7292
- Pages
- 1149-1154
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2877635
- OpenAlex
- W2323566388
- Cited by
- 1,136
- References
- 53
- Citations by year
- 2026: 27 · 2025: 40 · 2024: 53 · 2023: 45 · 2022: 53 · 2021: 72 · 2020: 82 · 2019: 81 · 2018: 78 · 2017: 74 · 2016: 78 · 2015: 76 · 2014: 78 · 2013: 107 · 2012: 73
- FWCI
- 100.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK072522)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- pancreatic beta-cell regeneration, beta-cell ablation, diphtheria toxin, insulin therapy, lineage tracing, diabetes treatment, transgenic mouse model, endocrine differentiation
- MeSH terms
- Insulin Secretion, Animals, Cell Count, Cell Differentiation, Diphtheria Toxin, Female, Glucagon, Humans, Insulin, Male, Mice, Transgenic, Regeneration, Biomarkers, Cell Death, Cell Lineage, Cell Proliferation, Glucagon-Secreting Cells, Insulin-Secreting Cells, Mice, Rats, Cell Transdifferentiation, Cellular Reprogramming
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