Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-09

AUTHORS

A. Willcox, S. J. Richardson, A. J. Bone, A. K. Foulis, N. G. Morgan

ABSTRACT

AIMS/HYPOTHESIS: In adults, the rate of beta cell replication is normally very low, but recent evidence suggests that it may increase during insulitis. We therefore studied tissue from donors with recent-onset type 1 diabetes to establish whether islet cell proliferation is increased during the disease process. METHODS: Paraffin-embedded pancreatic sections from ten donors with recent-onset type 1 diabetes and a range of relevant controls were stained by immunohistochemical techniques with antibodies against the proliferation markers Ki67 and minichromosome maintenance protein-2 (MCM-2). A combination staining technique involving immunoperoxidase and immunofluorescence methods was developed to quantify the numbers of alpha and beta cells with Ki67-positive nuclei and to investigate the relationship between insulitis and islet cell proliferation. RESULTS: In non-diabetic control donors, only 1.1 +/- 0.3% (mean +/- SEM) of islets contained one or more Ki67(+) islet cells, whereas this proportion was increased markedly in recent-onset type 1 diabetes (10.88 +/- 2.5%; p < 0.005). An equivalent increase in Ki67(+) staining occurred in alpha and beta cells and was correlated positively with the presence of insulitis. A significant increase in the labelling of islet cells from type 1 diabetic donors was also seen when MCM-2 staining was employed. Increased islet cell proliferation was not evident in three donors with longer duration type 1 diabetes or in ten type 2 diabetic donors. CONCLUSIONS/INTERPRETATION: Alpha and beta cells undergo a marked increase in proliferation during the progression of type 1 diabetes in humans. The results imply that islet cell proliferation is re-initiated in response to the autoimmune attack associated with type 1 diabetes. More... »

PAGES

2020-2028

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00125-010-1817-6

DOI

http://dx.doi.org/10.1007/s00125-010-1817-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043959469

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20532863


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