Expression of endoplasmic reticulum stress markers in the islets of patients with type 1 diabetes.
OBJECTIVE
Endoplasmic reticulum (ER) stress may play a role in cytokine-mediated beta cell death in type 1 diabetes, but it remains controversial whether ER stress markers are present in islets from type 1 diabetic individuals. Therefore, we evaluated by immunostaining the expression of markers of the three main branches of the ER stress response in islets from 13 individuals with and 15 controls without type 1 diabetes (eight adults and seven children).


METHODS
Antibodies against the ER stress markers C/EBP homologous protein (CHOP), immunoglobulin heavy chain (BIP) and X-box binding protein 1 (XBP-1) were validated using HeLa cells treated with the ER stressor thapsigargin. These antibodies were then used to stain serial sections of paraffin-embedded pancreas from type 1 diabetic and non-diabetic individuals; samples were also immunostained for CD45, insulin and glucagon. Immunostaining intensities of the ER stress markers were quantified using a software-based, unbiased quantitative approach.


RESULTS
Islets from individuals with type 1 diabetes showed increased levels of CHOP and, at least for insulitis-positive and beta cell-containing islets, BIP. XBP-1 expression was not, however, increased.


CONCLUSIONS
Islet cells from individuals with type 1 diabetes display a partial ER stress response, with evidence of the induction of some, but not all, components of the unfolded protein response.
Laboratory of Experimental Medicine, Medical Faculty, Université Libre de Bruxelles, CP-618, Route de Lennik 808, 1070 Brussels, Belgium.
I
I
Marhfour
X M
XM
Lopez
D
D
Lefkaditis
I
I
Salmon
F
F
Allagnat
S J
SJ
Richardson
N G
NG
Morgan
D L
DL
Eizirik
D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D004268:DNA-Binding Proteins / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000473:pathology*; D000071701:Regulatory Factor X Transcription Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000071717:X-Box Binding Protein 1; D055815:Young Adult
D015415:Biomarkers; C497249:DDIT3 protein, human; D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D051742:Transcription Factor CHOP