Changes in expression of IL-1 beta influenced proteins in transplanted islets during development of diabetes in diabetes-prone BB rats.
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.
Sparre
T
T
Steno Diabetes Center, Gentofte, Denmark. tspa@steno.dk
Christensen
U Bjerre
UB
Gotfredsen
C F
CF
Larsen
P Mose
PM
Fey
S J
SJ
Hjernø
K
K
Roepstorff
P
P
Pociot
F
F
Karlsen
A E
AE
Nerup
J
J
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
D007375:Interleukin-1; D012333:RNA, Messenger