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B-cell loss and B-cell apoptosis in human type 2 diabetes are related to islet amyloid deposition

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journal contribution
posted on 01.06.2011, 00:00 authored by C Jurgens, M Toukatly, C Fligner, J Udayasankar, S Subramanian, S Zraika, Kathryn Aston-MourneyKathryn Aston-Mourney, D Carr, P Westermark, G Westermark, S Kahn, R Hull
Amyloid deposition and reduced β-cell mass are pathological hallmarks of the pancreatic islet in type 2 diabetes; however, whether the extent of amyloid deposition is associated with decreased β-cell mass is debated. We investigated the possible relationship and, for the first time, determined whether increased islet amyloid and/or decreased β-cell area quantified on histological sections is correlated with increased β-cell apoptosis. Formalin-fixed, paraffin-embedded human pancreas sections from subjects with (n = 29) and without (n = 39) diabetes were obtained at autopsy (64 ± 2 and 70 ± 4 islets/subject, respectively). Amyloid and β cells were visualized by thioflavin S and insulin immunolabeling. Apoptotic β cells were detected by colabeling for insulin and by TUNEL. Diabetes was associated with increased amyloid deposition, decreased -cell area, and increased β-cell βapoptosis, as expected. There was a strong inverse correlation between β-cell area and amyloid deposition (r=0.42, P < 0.001). β-Cell area was selectively reduced in individual amyloid-containing islets from diabetic subjects, compared with control subjects, but amyloid-free islets had β-cell area equivalent to islets from control subjects. Increased amyloid deposition was associated with β-cell apoptosis (r= 0.56, P < 0.01). Thus, islet amyloid is associated with decreased β-cell area and increased β-cell apoptosis, suggesting that islet myloid deposition contributes to the decreased β-cell mass that characterizes type 2 diabetes.

History

Journal

American journal of clinical pathology

Volume

178

Issue

6

Pagination

2632 - 2640

Publisher

American Society for Clinical Pathology

Location

Birmingham, Ala.

ISSN

0002-9173

eISSN

1943-7722

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2011, American Society for Investigative Pathology