title: Changes in expression of IL-1 beta influenced proteins in transplanted islets during development of diabetes in diabetes-prone BB rats.
abstract: OBJECTIVE
  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-1 beta 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 S(35)-methionine for 2-DGE. The 82 proteins were re-localised and followed. In addition, transplants were examined for expression of IL-1 beta 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-1 beta in vitro. Highest expression of IL-1 beta mRNA was found at the onset of diabetes.
  
  
  CONCLUSIONS
  IL-1 beta-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.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. tspa@steno.dk
authors.forename: T
authors.initials: T
authors.lastname: Sparre
authors.forename: U Bjerre
authors.initials: UB
authors.lastname: Christensen
authors.forename: C F
authors.initials: CF
authors.lastname: Gotfredsen
authors.forename: P Mose
authors.initials: PM
authors.lastname: Larsen
authors.forename: S J
authors.initials: SJ
authors.lastname: Fey
authors.forename: K
authors.initials: K
authors.lastname: Hjernø
authors.forename: P
authors.initials: P
authors.lastname: Roepstorff
authors.forename: F
authors.initials: F
authors.lastname: Pociot
authors.forename: A E
authors.initials: AE
authors.lastname: Karlsen
authors.forename: J
authors.initials: J
authors.lastname: Nerup
mesh_terms: D000818:Animals; D002469:Cell Separation / Q000379:methods; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000276:immunology*; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000235:genetics*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011913:Rats, Inbred BB
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger