ArticleDiabetes2025
Loss of Insulin-Positive Cell Clusters Precedes the Decrease in Islet Frequency and β-Cell Area in Type 1 Diabetes.
Article in Diabetes, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Intra-Islet Paracrine Regulation of Glucagon Secretion During Hypoglycemia, Euglycemia, and Hyperglycemia.Annals of the New York Academy of Sciences · 2026Review
- Deep learning-powered quantification of endocrine cells and CD3Diabetologia · 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
- Imaging mass cytometry reveals functional and immunological changes during type 1 diabetes progression in human pancreata.Nature metabolism · 2026Article
- Mapping histologic and functional maturation of human endocrine pancreas across early postnatal periods.Nature communications · 2026Article
- Preservation of pancreatic endocrine and peri-islet exocrine capillary networks in type 2 diabetes.JCI insight · 2026Article
- 3D imaging of an entire pancreas shows inverse proportions of extra-islet versus islet-associated β cells in late-onset type 1 diabetes.Science advances · 2026Article
- Virtual multiplex staining of the pancreatic islets across type 1 diabetes progression using a Schrödinger bridge.bioRxiv : the preprint server for biology · 2026Article
- Integrated histopathology of the human pancreas throughout stages of type 1 diabetes progression.Nature communications · 2026Article
- 3D imaging of human pancreas suggests islet size and endocrine composition influence their loss in type 1 diabetes.Nature communications · 2025Article
- Small things matter: Lack of extraislet β cells in type 1 diabetes.Science advances · 2025Article
- Sweating the Small Stuff: A Closer Look at the Endocrine Pancreas Throughout Stages of Type 1 Diabetes Progression.Diabetes · 2025Article
- A mathematical model of insulin action on acinar tissue linking histology and radiological imaging of the pancreas.Frontiers in endocrinology · 2025Article
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13 authors.
Funding
Abstract
In type 1 diabetes (T1D), insulin (INS) deficiency results from immune-mediated destruction of β-cells. The majority of functional β-cell mass is typically lost within months to years of disease diagnosis, but the timing and nature of this loss, particularly in early disease stages, remain unclear. We developed a whole-slide scanned image analysis pipeline for semiautomated quantitation of endocrine area, islet frequency, interislet distance, and endocrine object size distribution in 145 human pancreata from 60 donors without diabetes, 19 donors with single autoantibody positivity, 10 with multiple autoantibody positivity (mAAb+), 16 with recent-onset T1D (duration 0-1 year), 23 with medium-duration T1D (1-7 years), and 17 with long-duration T1D (≥7 years). We observed age-related differences in endocrine composition and islet frequency in pancreata from donors without diabetes. Age-corrected data revealed decreased islet frequency and greater interislet distance in the T1D pancreas. INS+ single cells (≤10 μm), cell clusters (>10 to <35 μm), and small- and medium-sized islets (35-100 and 100-200 μm, respectively) were significantly lost at T1D onset, whereas large INS+ islets (>200 μm) were preserved. Moreover, changes in endocrine composition also occurred in pancreata from mAAb+ donors, including a significant decrease in the INS+ islet fraction. These data suggest preferential loss of INS+ small endocrine objects early in T1D development. ARTICLE HIGHLIGHTS: Understanding the timing and nature of β-cell loss is essential for developing effective strategies to interrupt type 1 diabetes progression. Which types of islets, in terms of size and cellular composition, are lost first during disease development? Insulin-positive single cells and cell clusters are lost before large islets during disease development. Insulin-positive single cells and cell clusters might be more susceptible to destruction in type 1 diabetes.
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