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

• Published in: Diabetologia 2012-09, Vol.55 (9), p.2417-2420
• Main Authors: Marhfour, I., Lopez, X. M., Lefkaditis, D., Salmon, I., Allagnat, F., Richardson, S. J., Morgan, N. G., Eizirik, D. L.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Antibodies; Apoptosis; Biological and medical sciences; Biomarkers - metabolism; Child; Cytokines; Diabetes; Diabetes Mellitus, Type 1 - metabolism; Diabetes Mellitus, Type 1 - pathology; Diabetes. Impaired glucose tolerance; DNA-Binding Proteins - metabolism; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Expression Regulation; Glucagon; Human Physiology; Humans; Immunoglobulins; Insulin; Internal Medicine; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Male; Males; Medical sciences; Medicine; Medicine & Public Health; Metabolic Diseases; Middle Aged; Pancreas - pathology; Photonics; Proteins; Regulatory Factor X Transcription Factors; Short Communication; Software; Transcription Factor CHOP - metabolism; Transcription Factors - metabolism; X-Box Binding Protein 1; Young Adult
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-012-2604-3

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.