Small things matter: Lack of extraislet β cells in type 1 diabetes
Recent three-dimensional (3D) analyses reported an abundance of small β cell-rich endocrine objects (EOs) in the human pancreas. Here, we used archival, immunolabeled 2D pancreas sections to assess morphological EO parameters in donors with or without type 1 diabetes (T1D), varying in age and disease duration. We confirm that abundant small, insulin-positive EOs are present in donors without diabetes and comprise most of the pancreatic endocrine area in early life. Small EOs are virtually absent in individuals with T1D, and this effect is most pronounced in children diagnosed with T1D in their earliest years. We conclude that extraislet β cells are affected in T1D development, and their early loss is a characteristic feature. This finding has important implications, which will inform future screening and treatment strategies for T1D.
Authors
- Christine S. Flaxman (ORCID: https://orcid.org/0009-0002-1144-7767)
- Pia Leete (ORCID: https://orcid.org/0000-0002-4013-0040)
- Kathryn Murrall (ORCID: https://orcid.org/0009-0009-3370-6767)
- Noel G. Morgan (ORCID: https://orcid.org/0000-0003-1537-8113)
- Irina Kusmartseva (ORCID: https://orcid.org/0000-0003-2614-0813)
- Susan B. Hunter (ORCID: https://orcid.org/0009-0002-4398-6204)
- Pouria Akhbari (ORCID: https://orcid.org/0000-0002-4127-9058)
- Rebecca C. Wyatt (ORCID: https://orcid.org/0000-0003-3345-3383)
- Sarah J. Richardson (ORCID: https://orcid.org/0000-0002-1160-6062)
- Isabel Burn (ORCID: https://orcid.org/0009-0008-7180-706X)
- Teifion Luckett (ORCID: https://orcid.org/0009-0003-4675-2830)
- Christiana Lekka (ORCID: https://orcid.org/0000-0003-0188-7590)
- James Shaw (ORCID: https://orcid.org/0000-0002-2893-3211)
- Elena Osokina
Institutions
- Sandia National Laboratories California (US)
- University of Exeter (GB)
- University of Florida (US)
- Bridge University (SS)
- Newcastle University (GB)
- Florida College (US)
Publication Details
- Journal
- Science Advances
- Published
- 2025-11-12
- DOI
- https://doi.org/10.1126/sciadv.adz2251
- Citations
- 3
- Primary Topic
- Pancreatic function and diabetes
- Type
- article
- Field-Weighted Citation Impact
- 6.02
Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- Seattle Children's Research Institute
- National Institute for Health and Care Research
- Department of Health and Social Care
- Diabetes UK
- University of Exeter