Characterisation of the endocrine pancreas in type 1 diabetes: islet size is maintained but islet number is markedly reduced

The Journal of Pathology. Clinical Research
Peter SeironOlle Korsgren

Abstract

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 ~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 cell...Continue Reading

References

Apr 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·L OrciR H Unger
Jul 1, 1973·Clinical Endocrinology·I Doniach, A G Morgan
May 13, 1999·The Journal of Biological Chemistry·J C JonasGordon C Weir
May 25, 2010·Seminars in Immunopathology·Patrick A RoweMark Atkinson
Aug 11, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Anna PisaniaSusan Bonner-Weir
Sep 30, 2010·Diabetes·Susan Bonner-WeirArun Sharma
Mar 13, 2012·Nature Genetics·Chutima TalchaiDomenico Accili
Apr 10, 2013·Diabetes·H Siebe SpijkerEelco J P de Koning
Nov 13, 2013·Diabetes·Teresa MezzaRohit N Kulkarni
Nov 20, 2015·Diabetes·Martha Campbell-ThompsonMark Atkinson
Dec 30, 2015·The Journal of Clinical Endocrinology and Metabolism·Francesca CintiDomenico Accili
Dec 29, 2016·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Olli HelminenTuomo J Karttunen
Mar 8, 2018·Cell Reports·Marcela BrissovaAlvin C Powers

Citations

Nov 2, 2019·International Journal of Molecular Sciences·Ciro SalinnoMostafa Bakhti
Jul 23, 2020·Nature Metabolism·Stephan SachsHeiko Lickert

Related Concepts

Biopsy
Diabetes Mellitus, Insulin-Dependent
Disease Susceptibility
Insulin
Islets of Langerhans
Pancreas
Structure of Alpha Cell of Islet
Structure of Beta Cell of Islet
Transcription Factor
Research Subject

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