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What Is the Sweetest UPR Flavor for the β-cell? That Is the Question

Unfolded protein response (UPR) is a process conserved from yeasts to mammals and, based on the generally accepted dogma, helps the secretory performance of a cell, by improving its capacity to cope with a burden in the endoplasmic reticulum (ER). The ER of β-cells, “professional secretory cells”, h...

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Autores principales: Lenghel, Alina, Gheorghita, Alina Maria, Vacaru, Andrei Mircea, Vacaru, Ana-Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891099/
https://www.ncbi.nlm.nih.gov/pubmed/33613449
http://dx.doi.org/10.3389/fendo.2020.614123
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author Lenghel, Alina
Gheorghita, Alina Maria
Vacaru, Andrei Mircea
Vacaru, Ana-Maria
author_facet Lenghel, Alina
Gheorghita, Alina Maria
Vacaru, Andrei Mircea
Vacaru, Ana-Maria
author_sort Lenghel, Alina
collection PubMed
description Unfolded protein response (UPR) is a process conserved from yeasts to mammals and, based on the generally accepted dogma, helps the secretory performance of a cell, by improving its capacity to cope with a burden in the endoplasmic reticulum (ER). The ER of β-cells, “professional secretory cells”, has to manage tremendous amounts of insulin, which elicits a strong pressure on the ER intrinsic folding capacity. Thus, the constant demand for insulin production results in misfolded proinsulin, triggering a physiological upregulation of UPR to restore homeostasis. Most diabetic disorders are characterized by the loss of functional β-cells, and the pathological side of UPR plays an instrumental role. The transition from a homeostatic to a pathological UPR that ultimately leads to insulin-producing β-cell decay entails complex cellular processes and molecular mechanisms which remain poorly described so far. Here, we summarize important processes that are coupled with or driven by UPR in β-cells, such as proliferation, inflammation and dedifferentiation. We conclude that the UPR comes in different “flavors” and each of them is correlated with a specific outcome for the cell, for survival, differentiation, proliferation as well as cell death. All these greatly depend on the way UPR is triggered, however what exactly is the switch that favors the activation of one UPR as opposed to others is largely unknown. Substantial work needs to be done to progress the knowledge in this important emerging field as this will help in the development of novel and more efficient therapies for diabetes.
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spelling pubmed-78910992021-02-19 What Is the Sweetest UPR Flavor for the β-cell? That Is the Question Lenghel, Alina Gheorghita, Alina Maria Vacaru, Andrei Mircea Vacaru, Ana-Maria Front Endocrinol (Lausanne) Endocrinology Unfolded protein response (UPR) is a process conserved from yeasts to mammals and, based on the generally accepted dogma, helps the secretory performance of a cell, by improving its capacity to cope with a burden in the endoplasmic reticulum (ER). The ER of β-cells, “professional secretory cells”, has to manage tremendous amounts of insulin, which elicits a strong pressure on the ER intrinsic folding capacity. Thus, the constant demand for insulin production results in misfolded proinsulin, triggering a physiological upregulation of UPR to restore homeostasis. Most diabetic disorders are characterized by the loss of functional β-cells, and the pathological side of UPR plays an instrumental role. The transition from a homeostatic to a pathological UPR that ultimately leads to insulin-producing β-cell decay entails complex cellular processes and molecular mechanisms which remain poorly described so far. Here, we summarize important processes that are coupled with or driven by UPR in β-cells, such as proliferation, inflammation and dedifferentiation. We conclude that the UPR comes in different “flavors” and each of them is correlated with a specific outcome for the cell, for survival, differentiation, proliferation as well as cell death. All these greatly depend on the way UPR is triggered, however what exactly is the switch that favors the activation of one UPR as opposed to others is largely unknown. Substantial work needs to be done to progress the knowledge in this important emerging field as this will help in the development of novel and more efficient therapies for diabetes. Frontiers Media S.A. 2021-01-19 /pmc/articles/PMC7891099/ /pubmed/33613449 http://dx.doi.org/10.3389/fendo.2020.614123 Text en Copyright © 2021 Lenghel, Gheorghita, Vacaru and Vacaru http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Lenghel, Alina
Gheorghita, Alina Maria
Vacaru, Andrei Mircea
Vacaru, Ana-Maria
What Is the Sweetest UPR Flavor for the β-cell? That Is the Question
title What Is the Sweetest UPR Flavor for the β-cell? That Is the Question
title_full What Is the Sweetest UPR Flavor for the β-cell? That Is the Question
title_fullStr What Is the Sweetest UPR Flavor for the β-cell? That Is the Question
title_full_unstemmed What Is the Sweetest UPR Flavor for the β-cell? That Is the Question
title_short What Is the Sweetest UPR Flavor for the β-cell? That Is the Question
title_sort what is the sweetest upr flavor for the β-cell? that is the question
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891099/
https://www.ncbi.nlm.nih.gov/pubmed/33613449
http://dx.doi.org/10.3389/fendo.2020.614123
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