ArticleCell2012
Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure.
Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 885 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
885 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,383 citations in OpenAlex.
- Effects of continuous positive airway pressure therapy duration on patients with obstructive sleep apnoea and type 2 diabetes mellitus: a systematic review and meta-analysis.BMJ open respiratory research · 2026Pooled it
- 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
- Systematic Comparison of High-Fat Diet- and Streptozotocin-Induced Prediabetic Obese C57BL/6J Mouse Models: A Sex-Based Protocol Optimization Study.Diabetes, obesity & metabolism · 2026Article
- BAF60A governs beta cell identity to control systemic glucose homeostasis.Diabetologia · 2026Article
- Adipocyte-derived exosomal ANGPTL2 promotes beta cell dysfunction via the EIF2α/ATF4/CHOP stress pathway in mice.Diabetologia · 2026Article
- Harnessing Endogenous Plasticity Rather than Reprogramming of Mature Cells Will Advance Regenerative Medicine, Cancer Treatment and Rejuvenation.Stem cell reviews and reports · 2026Review
- Human β-Cell Dedifferentiation and Diabetes.Journal of diabetes · 2026Review
- Impact of Sex on Age-Related Changes in Pancreatic Islet Morphology and Beta-Cell Plasticity in Mice.International journal of molecular sciences · 2026Article
- CRISPR Technologies in Type 2 Diabetes: From Mechanistic Insights to Therapeutic Discovery.International journal of molecular sciences · 2026Review
- The comparative cell physiology of stem cell-derived and primary human β cells.Nature reviews. Endocrinology · 2026Review
- Hepatic translational rewiring in insulin deficiency identifies Reg3α as an insulin-independent glucoregulatory factor.Endocrinology · 2026Article
- GPR180 deficiency impairs mitochondrial function and insulin secretion in pancreatic β-cells.Molecular metabolism · 2026Article
- Understanding development and cellular plasticity in the pancreas in health and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Interpretable single-cell machine learning identifies PINK1-centred mitophagy as a determinant of metabolic fitness in type 2 diabetes.Acta diabetologica · 2026Article
- Metabolic state determines the brain and direct islet effects of liraglutide on enhanced insulin secretion.Diabetologia · 2026Article
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- β-Cell Dysfunction in COVID-19 and Post-COVID Syndrome: Molecular Mechanisms Linking Inflammation, Oxidative Stress, and Insulin Secretion.International journal of molecular sciences · 2026Review
- Recent advances in pancreatic β-cell dysfunction in type 2 diabetes mellitus: Intracellular stress and dedifferentiation.Journal of diabetes investigation · 2026Article
- Temporal single-cell transcriptional dynamics of murine pancreatic islet remodeling during hyperglycaemia progression.Molecular metabolism · 2026Article
- Adverse effect of age on pancreatic islet morphology, islet cell turnover and lineage-labelled hormone expression in mice.Journal of endocrinological investigation · 2026Article
825 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
Diabetes is associated with β cell failure. But it remains unclear whether the latter results from reduced β cell number or function. FoxO1 integrates β cell proliferation with adaptive β cell function. We interrogated the contribution of these two processes to β cell dysfunction, using mice lacking FoxO1 in β cells. FoxO1 ablation caused hyperglycemia with reduced β cell mass following physiologic stress, such as multiparity and aging. Surprisingly, lineage-tracing experiments demonstrated that loss of β cell mass was due to β cell dedifferentiation, not death. Dedifferentiated β cells reverted to progenitor-like cells expressing Neurogenin3, Oct4, Nanog, and L-Myc. A subset of FoxO1-deficient β cells adopted the α cell fate, resulting in hyperglucagonemia. Strikingly, we identify the same sequence of events as a feature of different models of murine diabetes. We propose that dedifferentiation trumps endocrine cell death in the natural history of β cell failure and suggest that treatment of β cell dysfunction should restore differentiation, rather than promoting β cell replication.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.