Changes in expression of IL-1β influenced proteins in transplanted islet during development of diabetes in diabetes-prone BB rats

T. Sparre*, U. Bjerre Christensen, C. F. Gotfredsen, P. Mose Larsen, S. J. Fey, K. Hjernø, P. Roepstorff, F. Pociot, A. E. Karlsen, J. Nerup

*Corresponding author for this work
21 Citations (Scopus)

Abstract

Aims/hypothesis. Type 1 diabetes mellitus is a multifactorial autoimmune disease characterised by selective destruction of beta cells in the islets of Langerhans. We have previously shown that IL-1β modulates beta cell function, causes beta cell death and induces expression changes in 82 out of 1815 protein spots detected by two-dimensional gel electrophoresis (2-DGE) in diabetes-prone bio-breeding (BB-DP) rat islets in vitro. The aim of this study was to describe the relevance of these proteins in the development of diabetes in vivo. Methods. Syngeneic neonatal islets (n=200) were transplanted under the kidney capsule of 30-day-old BB-DP and control rats, removed to different time points after transplantation or at the onset of diabetes, and metabolically labelled with S35-methionine for 2-DGE. The 82 proteins were re-localised and followed. In addition, transplants were examined for expression of IL-1β mRNA by in situ hybridisation. Results. All 82 proteins could be re-localised in all syngeneic transplants from BB-DP and control rats. A total of 60 of the 82 proteins were changed during development of diabetes. Of the 82 proteins, 32 were changed in expression at the onset of diabetes compared to non-diabetic BB-DP rats, and 25 of these were changed as by IL-1β in vitro. Highest expression of IL-1β mRNA was found at the onset of diabetes. Conclusions/interpretation. IL-1β-induced protein expression changes in islets in vitro also occur in vivo and change in a complex pattern during the development of diabetes in the BB-DP rat. No single protein seems to be responsible for the development of diabetes, but rather the cumulative numbers of changes seem to interfere with the intracellular stability of the beta cell.

Original languageEnglish
JournalDiabetologia
Volume47
Issue number5
Pages (from-to)892-908
Number of pages17
ISSN0012-186X
DOIs
Publication statusPublished - 1 May 2004

Keywords

  • BB rat
  • Cytokines
  • Diabetes
  • IL-1β
  • Islet
  • Mass spectrometry
  • Pathogenesis
  • Proteome analysis
  • Transplantation
  • Two-dimensional gel electrophoresis

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