title: Role of the unfolded protein response in β cell compensation and failure during diabetes.
abstract: Pancreatic β cell failure leads to diabetes development. During disease progression, β cells adapt their secretory capacity to compensate the elevated glycaemia and the peripheral insulin resistance. This compensatory mechanism involves a fine-tuned regulation to modulate the endoplasmic reticulum (ER) capacity and quality control to prevent unfolded proinsulin accumulation, a major protein synthetized within the β cell. These signalling pathways are collectively termed unfolded protein response (UPR). The UPR machinery is required to preserve ER homeostasis and β cell integrity. Moreover, UPR actors play a key role by regulating ER folding capacity, increasing the degradation of misfolded proteins, and limiting the mRNA translation rate. Recent genetic and biochemical studies on mouse models and human UPR sensor mutations demonstrate a clear requirement of the UPR machinery to prevent β cell failure and increase β cell mass and adaptation throughout the progression of diabetes. In this review we will highlight the specific role of UPR actors in β cell compensation and failure during diabetes.
authors.affiliation: European Genomic Institute for Diabetes (EGID), CNRS UMR 8199, Lille 2 University of Health and Law, 59000 Lille, France.
authors.forename: Nabil
authors.initials: N
authors.lastname: Rabhi
authors.affiliation: European Genomic Institute for Diabetes (EGID), CNRS UMR 8199, Lille 2 University of Health and Law, 59000 Lille, France.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Salas
authors.affiliation: European Genomic Institute for Diabetes (EGID), CNRS UMR 8199, Lille 2 University of Health and Law, 59000 Lille, France ; Departments of Genomics of Common Disease, Hammersmith Hospital, Imperial College London, London, UK.
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.affiliation: European Genomic Institute for Diabetes (EGID), CNRS UMR 8199, Lille 2 University of Health and Law, 59000 Lille, France ; Laboratoire Bases Moléculaires et Modélisation du Diabète et de l'Obésité, Faculté de Médecine, Pôle Recherche, 59045 Lille, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Annicotte
mesh_terms: D052636:Allostasis; D000818:Animals; D003920:Diabetes Mellitus / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D018450:Disease Progression; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008954:Models, Biological; D014176:Protein Biosynthesis; D056811:Unfolded Protein Response
chemical_list: D007328:Insulin