title: Endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation.
abstract: Insulin-secreting pancreatic β-cells are extremely dependent on their endoplasmic reticulum (ER) to cope with the oscillatory requirement of secreted insulin to maintain normoglycemia. Insulin translation and folding rely greatly on the unfolded protein response (UPR), an array of three main signaling pathways designed to maintain ER homeostasis and limit ER stress. However, prolonged or excessive UPR activation triggers alternative molecular pathways that can lead to β-cell dysfunction and apoptosis. An increasing number of studies suggest a role of these pro-apoptotic UPR pathways in the downfall of β-cells observed in diabetic patients. Particularly, the past few years highlighted a cross talk between the UPR and inflammation in the context of both type 1 (T1D) and type 2 diabetes (T2D). In this article, we describe the recent advances in research regarding the interplay between ER stress, the UPR, and inflammation in the context of β-cell apoptosis leading to diabetes.
authors.affiliation: ULB Center for Diabetes ResearchUniversité Libre de Bruxelles (ULB), Brussels, Belgium.
authors.forename: Kira
authors.initials: K
authors.lastname: Meyerovich
authors.affiliation: Department of Cell and Developmental BiologyUniversidade de São Paulo, São Paulo, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Ortis
authors.affiliation: Department of Vascular SurgeryCentre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
authors.forename: Florent
authors.initials: F
authors.lastname: Allagnat
authors.affiliation: ULB Center for Diabetes ResearchUniversité Libre de Bruxelles (ULB), Brussels, Belgium akupperc@ulb.ac.be.
authors.forename: Alessandra K
authors.initials: AK
authors.lastname: Cardozo
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004198:Disease Susceptibility; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D056811:Unfolded Protein Response / Q000187:drug effects
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D018832:Molecular Chaperones; D016328:NF-kappa B; D048031:JNK Mitogen-Activated Protein Kinases
keywords: NF-kB; diabetes; inflammation; pancreatic beta cells; unfolded protein response