ArticleJCI insight2021
Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 58 citations in OpenAlex.
- Adipocyte-derived exosomal ANGPTL2 promotes beta cell dysfunction via the EIF2α/ATF4/CHOP stress pathway in mice.Diabetologia · 2026Article
- BAF60A governs beta cell identity to control systemic glucose homeostasis.Diabetologia · 2026Article
- Human β-Cell Dedifferentiation and Diabetes.Journal of diabetes · 2026Review
- Polystyrene Nanoplastics Drive β-Cell Dedifferentiation Through Dendritic Cell-Intrinsic MHC-I-Dependent Inflammatory Crosstalk.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- Transient Overexpression of pVHL Mediated by Adenoviral Vector Injection in Pancreatic Tissue Decreases Blood Glucose Levels in a Hypercaloric Diet-Induced Mouse Model of Type 2 Diabetes Mellitus.International journal of molecular sciences · 2026Article
- Review
- Zinc accumulation-induced integrated stress response triggers β-cell identity loss.Cell research · 2026Article
- Investigational treatments of β-cell failure and replacement.Diabetology international · 2026Review
- Ectopic fat distribution and its correlation with insulin resistance indices in non-obese individuals with type 2 diabetes.Acta diabetologica · 2026Article
- Single-cell RNA-seq and in vitro study reveal Fusobacterium nucleatum impairs β-cell identity in type 2 diabetes via the NF-κB-CDKN1C axis.Journal of translational medicine · 2026Article
- LDHA induces beta cell dedifferentiation in diabetes through metabolic and epigenetic reprogramming.Diabetologia · 2026Article
- Modelling the effects of human SUR1 R1420H variation on insulin secretory function using isogenic iPSC-derived pancreatic islets.Diabetologia · 2026Article
- SIRT1 Regulates Iron Metabolism to Attenuate β-Cell Dedifferentiation by Inhibiting FoxO1 Acetylation.Biological trace element research · 2026Article
- Osteocalcin induces phosphorylation of FOXO1 in human beta-cells and restores insulin expression under hyperglycemic conditions.Research square · 2025Article
- The Impact of Major and Minor Phytocannabinoids on the Maintenance and Function of INS-1 β-Cells Under High-Glucose and High-Lipid Conditions.Molecules (Basel, Switzerland) · 2025Article
- β-Cell Dedifferentiation in HOMA-βlow and HOMA-βhigh Subjects.The Journal of clinical endocrinology and metabolism · 2025Article
- DECORIN, a triceps-derived myokine, protects sorted β-cells and human islets against chronic inflammation associated with type 2 diabetes.Acta physiologica (Oxford, England) · 2025Article
- Article
- PAX4 gene delivery improves β-cell function in human islets of Type II diabetes.Regenerative medicine · 2024Article
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dedifferentiation has been implicated in β cell dysfunction and loss in rodent diabetes. However, the pathophysiological significance in humans remains unclear. To elucidate this, we analyzed surgically resected pancreatic tissues of 26 Japanese subjects with diabetes and 11 nondiabetic subjects, who had been overweight during adulthood but had no family history of diabetes. The diabetic subjects were subclassified into 3 disease stage categories, early, advanced, and intermediate. Despite no numerical changes in endocrine cells immunoreactive for chromogranin A (ChgA), diabetic islets showed profound β cell loss, with an increase in α cells without an increase in insulin and glucagon double-positive cells. The proportion of dedifferentiated cells that retain ChgA immunoreactivity without 4 major islet hormones was strikingly increased in diabetic islets and rose substantially during disease progression. The increased dedifferentiated cell ratio was inversely correlated with declining C-peptide index. Moreover, a subset of islet cells converted into exocrine-like cells during disease progression. These results indicate that islet remodeling with dedifferentiation is the underlying cause of β cell failure during the course of diabetes progression in humans.
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