Expression of endoplasmic reticulum stress markers in the islets of patients with type 1 diabetes

Diabetologia. 2012 Sep;55(9):2417-20. doi: 10.1007/s00125-012-2604-3. Epub 2012 Jun 15.


Aims/hypothesis: 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/interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis
  • Biomarkers / metabolism
  • Child
  • DNA-Binding Proteins / metabolism
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / pathology
  • Endoplasmic Reticulum Stress*
  • Female
  • Gene Expression Regulation
  • Humans
  • Islets of Langerhans / metabolism*
  • Islets of Langerhans / pathology
  • Male
  • Middle Aged
  • Pancreas / pathology*
  • Regulatory Factor X Transcription Factors
  • Transcription Factor CHOP / metabolism
  • Transcription Factors / metabolism
  • X-Box Binding Protein 1
  • Young Adult


  • Biomarkers
  • DDIT3 protein, human
  • DNA-Binding Proteins
  • Regulatory Factor X Transcription Factors
  • Transcription Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Transcription Factor CHOP