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Amyloid formation results in recurrence of hyperglycaemia following transplantation of human IAPP transgenic mouse islets

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journal contribution
posted on 01.01.2009, 00:00 authored by J Udayasankar, K Kodama, R Hull, S Zraika, Kathryn Aston-MourneyKathryn Aston-Mourney, S Subramanian, J Tong, M Faulenbach, J Vidal, S Kahn
Aims/hypothesis Islet transplantation is a potential cure for diabetes; however, rates of graft failure remain high. The aim of the present study was to determine whether amyloid deposition is associated with reduced beta cell volume in islet grafts and the recurrence of hyperglycaemia following islet transplantation.

Methods We transplanted a streptozotocin-induced mouse model of diabetes with 100 islets from human IAPP (which encodes islet amyloid polypeptide) transgenic mice that have the propensity to form islet amyloid (n = 8–12) or from non-transgenic mice that do not develop amyloid (n = 6–10) in sets of studies that lasted 1 or 6 weeks.

Results Plasma glucose levels before and for 1 week after transplantation were similar in mice that received transgenic or non-transgenic islets, and at that time amyloid was detected in all transgenic grafts and, as expected, in none of the non-transgenic grafts. However, over the 6 weeks following transplantation, plasma glucose levels increased in transgenic but remained stable in non-transgenic islet graft recipients (p < 0.05). At 6 weeks, amyloid was present in 92% of the transgenic grafts and in none of the non-transgenic grafts. Beta cell volume was reduced by 30% (p < 0.05), beta cell apoptosis was twofold higher (p < 0.05), and beta cell replication was reduced by 50% (p < 0.001) in transgenic vs non-transgenic grafts. In summary, amyloid deposition in islet grafts occurs prior to the recurrence of hyperglycaemia and its accumulation over time is associated with beta cell loss.

Conclusions/interpretation Islet amyloid formation may explain, in part, the non-immune loss of beta cells and recurrence of hyperglycaemia following clinical islet transplantation.

History

Journal

Diabetologia

Volume

52

Issue

1

Pagination

145 - 153

Publisher

Springer

Location

Heidelberg, Germany

ISSN

0012-186X

eISSN

1432-0428

Language

eng

Publication classification

C1.1 Refereed article in a scholarly journal

Copyright notice

2008, Springer-Verlag