ArticleThe Journal of clinical endocrinology and metabolism2016
Evidence of β-Cell Dedifferentiation in Human Type 2 Diabetes.
Article in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 361 papers.
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Who cites it
361 citing papers in PubMed, 536 citations in OpenAlex.
- Achieving Diabetes Remission Through Dietary Intervention: A 12-Month Randomized Controlled Trial of Caloric-Carbohydrate Restriction in Overweight Patients With Early-Stage Type 2 Diabetes Mellitus.Journal of diabetes research · 2026Trial
- Efficacy and safety of needle-free injection in patients with type 2 diabetes mellitus undergoing intensive insulin therapy: a randomized controlled trial based on the flash glucose monitoring system.Frontiers in endocrinology · 2025Trial
- Human β-Cell Dedifferentiation and Diabetes.Journal of diabetes · 2026Review
- Harnessing Endogenous Plasticity Rather than Reprogramming of Mature Cells Will Advance Regenerative Medicine, Cancer Treatment and Rejuvenation.Stem cell reviews and reports · 2026Review
- Differential Associations of Healthy Lifestyle Latent Classes with Glycemic Transitions in Prediabetes: An Observational Study Based on CHARLS.Healthcare (Basel, Switzerland) · 2026Article
- Determination of Expression and Relationships of Nedd4-Related E3 Ubiquitin Ligase-2 (NEDL2) and Ubiquitin Proteasome System Proteins in Developing Rat Pancreatic Tissue.Anatomia, histologia, embryologia · 2026Article
- The central role of the β-cell in diabetes: from monogenic forms to type 1, type 2, and gestational diabetes.Reviews in endocrine & metabolic disorders · 2026Review
- Reduced peroxisomal function increases insulin secretion, promotes insulin oxidation, and impairs β cell maturity.JCI insight · 2026Article
- Adverse effect of age on pancreatic islet morphology, islet cell turnover and lineage-labelled hormone expression in mice.Journal of endocrinological investigation · 2026Article
- Recent advances in pancreatic β-cell dysfunction in type 2 diabetes mellitus: Intracellular stress and dedifferentiation.Journal of diabetes investigation · 2026Article
- Mesenchymal Stem Cell-Derived Extracellular Vesicles Attenuate Diabetic β-Cell Apoptosis and Dedifferentiation by Delivering miR-4436.Tissue engineering and regenerative medicine · 2026Article
- Syntaxin-4, a key exocytosis mediating protein, shows heterogeneous expression in insulin-positive cells of human donors with new-onset and longer duration of type 1 diabetes: comparison with non-diabetic autoantibody-positive and -negative donors.Journal of molecular histology · 2026Article
- Review
- From pancreas and islet resources to diabetes insights.Diabetologia · 2026Review
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 2026Review
- SOX9: dosage- and context-dependent functions in pancreatic development and β-cell biology.Cell communication and signaling : CCS · 2026Review
- HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during liver aging.Research square · 2026Article
- eNAMPT induces alpha-cell mass expansion but impaired glucagon counter regulatory response.Endocrinology · 2026Article
- Proteomic analyses of human islets reveal potential markers of β cell dysfunction during prediabetes.JCI insight · 2026Article
- Zinc accumulation-induced integrated stress response triggers β-cell identity loss.Cell research · 2026Article
301 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
contextDiabetes is associated with a deficit of insulin-producing β-cells. Animal studies show that β-cells become dedifferentiated in diabetes, reverting to a progenitor-like stage, and partly converting to other endocrine cell types.
objectiveTo determine whether similar processes occur in human type 2 diabetes, we surveyed pancreatic islets from 15 diabetic and 15 nondiabetic organ donors.
designWe scored dedifferentiation using markers of endocrine lineage, β-cell-specific transcription factors, and a newly identified endocrine progenitor cell marker, aldehyde dehydrogenase 1A3.
resultsBy these criteria, dedifferentiated cells accounted for 31.9% of β-cells in type 2 diabetics vs 8.7% in controls, and for 16.8% vs 6.5% of all endocrine cells (P < .001). The number of aldehyde dehydrogenase 1A3-positive/hormone-negative cells was 3-fold higher in diabetics compared with controls. Moreover, β-cell-specific transcription factors were ectopically found in glucagon- and somatostatin-producing cells of diabetic subjects.
conclusionsThe data support the view that pancreatic β-cells become dedifferentiated and convert to α- and δ-"like" cells in human type 2 diabetes. The findings should prompt a reassessment of goals in the prevention and treatment of β-cell dysfunction.
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Registered trials
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