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Characterisation of the endocrine pancreas in type 1 diabetes: islet size is maintained but islet number is markedly reduced
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.ORCID iD: 0000-0002-1419-450X
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
Oslo Univ Hosp, Div Paediat & Adolescent Med, Oslo, Norway.
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2019 (English)In: The journal of pathology. Clinical research, ISSN 2056-4538, Vol. 5, no 4, p. 248-255Article in journal (Refereed) Published
Abstract [en]

Insulin deficiency in type 1 diabetes (T1D) is generally considered a consequence of immune-mediated specific beta-cell loss. Since healthy pancreatic islets consist of similar to 65% beta cells, this would lead to reduced islet size, while the number of islets per pancreas volume (islet density) would not be affected. In this study, we compared the islet density, size, and size distribution in biopsies from subjects with recent-onset or long-standing T1D, with that in matched non-diabetic subjects. The results presented show preserved islet size and islet size distribution, but a marked reduction in islet density in subjects with recent onset T1D compared with non-diabetic subjects. No further reduction in islet density occurred with increased disease duration. Insulin-negative islets in T1D subjects were dominated by glucagon-positive cells that often had lost the alpha-cell transcription factor ARX while instead expressing PDX1, normally only expressed in beta cells within the islets. Based on our findings, we propose that failure to establish a sufficient islet number to reach the beta-cell mass needed to cope with episodes of increased insulin demand contributes to T1D susceptibility. Exhaustion induced by relative lack of beta cells could then potentially drive beta-cell dedifferentiation to alpha-cells, explaining the preserved islet size observed in T1D compared to controls.

Place, publisher, year, edition, pages
2019. Vol. 5, no 4, p. 248-255
Keywords [en]
type 1 diabetes, human, pancreas
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-397132DOI: 10.1002/cjp2.140ISI: 000492906100004PubMedID: 31493350OAI: oai:DiVA.org:uu-397132DiVA, id: diva2:1374044
Funder
Swedish Child Diabetes FoundationEU, FP7, Seventh Framework Programme, 261441EXODIAB - Excellence of Diabetes Research in SwedenSwedish Society for Medical Research (SSMF), K2015‐54X‐12219‐19‐4, 921‐2014‐7054Ernfors FoundationNovo NordiskÅke Wiberg FoundationTore Nilsons Stiftelse för medicinsk forskning
Note

Knut Dahl‐Jørgensen, Oskar Skog and Olle Korsgren share senior authorship. Peter Seiron and Anna Wiberg contributed equally to this work.

Available from: 2019-11-28 Created: 2019-11-28 Last updated: 2019-11-28Bibliographically approved

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Seiron, PeterWiberg, AnnaKuric, EnidaSkog, OskarKorsgren, Olle

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