Role of the Unfolded Protein Response in β Cell Compensation and Failure during Diabetes

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 (...

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Main Authors: Nabil Rabhi, Elisabet Salas, Philippe Froguel, Jean-Sébastien Annicotte
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2014/795171
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author Nabil Rabhi
Elisabet Salas
Philippe Froguel
Jean-Sébastien Annicotte
author_facet Nabil Rabhi
Elisabet Salas
Philippe Froguel
Jean-Sébastien Annicotte
author_sort Nabil Rabhi
collection DOAJ
description 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.
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spelling doaj-art-3a6ee7047cb84b0ea1f0482f6cab38de2025-08-20T03:35:51ZengWileyJournal of Diabetes Research2314-67452314-67532014-01-01201410.1155/2014/795171795171Role of the Unfolded Protein Response in β Cell Compensation and Failure during DiabetesNabil Rabhi0Elisabet Salas1Philippe Froguel2Jean-Sébastien Annicotte3European Genomic Institute for Diabetes (EGID), CNRS UMR 8199, Lille 2 University of Health and Law, 59000 Lille, FranceEuropean Genomic Institute for Diabetes (EGID), CNRS UMR 8199, Lille 2 University of Health and Law, 59000 Lille, FranceEuropean Genomic Institute for Diabetes (EGID), CNRS UMR 8199, Lille 2 University of Health and Law, 59000 Lille, FranceEuropean Genomic Institute for Diabetes (EGID), CNRS UMR 8199, Lille 2 University of Health and Law, 59000 Lille, FrancePancreatic 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.http://dx.doi.org/10.1155/2014/795171
spellingShingle Nabil Rabhi
Elisabet Salas
Philippe Froguel
Jean-Sébastien Annicotte
Role of the Unfolded Protein Response in β Cell Compensation and Failure during Diabetes
Journal of Diabetes Research
title Role of the Unfolded Protein Response in β Cell Compensation and Failure during Diabetes
title_full Role of the Unfolded Protein Response in β Cell Compensation and Failure during Diabetes
title_fullStr Role of the Unfolded Protein Response in β Cell Compensation and Failure during Diabetes
title_full_unstemmed Role of the Unfolded Protein Response in β Cell Compensation and Failure during Diabetes
title_short Role of the Unfolded Protein Response in β Cell Compensation and Failure during Diabetes
title_sort role of the unfolded protein response in β cell compensation and failure during diabetes
url http://dx.doi.org/10.1155/2014/795171
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