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Diabetologia. 2010 Sep;53(9):2020-8. doi: 10.1007/s00125-010-1817-6. Epub 2010 Jun 9.

Evidence of increased islet cell proliferation in patients with recent-onset type 1 diabetes.

Author information

1
Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry (University of Exeter), Tamar Science Park, Derriford, Plymouth, UK.

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.

PMID:
20532863
DOI:
10.1007/s00125-010-1817-6
[Indexed for MEDLINE]

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