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Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets

Inappropriate food intake-related obesity and more importantly, visceral adiposity, are major risk factors for the onset of type 2 diabetes. Evidence is emerging that nutriment-induced β-cell dysfunction could be related to indirect induction of a state of low grade inflammation. Our aim was to stud...

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Autores principales: Chentouf, Myriam, Dubois, Gregor, Jahannaut, Céline, Castex, Françoise, Lajoix, Anne Dominique, Gross, René, Peraldi-Roux, Sylvie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149618/
https://www.ncbi.nlm.nih.gov/pubmed/21826222
http://dx.doi.org/10.1371/journal.pone.0022954
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author Chentouf, Myriam
Dubois, Gregor
Jahannaut, Céline
Castex, Françoise
Lajoix, Anne Dominique
Gross, René
Peraldi-Roux, Sylvie
author_facet Chentouf, Myriam
Dubois, Gregor
Jahannaut, Céline
Castex, Françoise
Lajoix, Anne Dominique
Gross, René
Peraldi-Roux, Sylvie
author_sort Chentouf, Myriam
collection PubMed
description Inappropriate food intake-related obesity and more importantly, visceral adiposity, are major risk factors for the onset of type 2 diabetes. Evidence is emerging that nutriment-induced β-cell dysfunction could be related to indirect induction of a state of low grade inflammation. Our aim was to study whether hyperphagia associated obesity could promote an inflammatory response in pancreatic islets leading to ß-cell dysfunction. In the hyperphagic obese insulin resistant male Zucker rat, we measured the level of circulating pro-inflammatory cytokines and estimated their production as well as the expression of their receptors in pancreatic tissue and β-cells. Our main findings concern intra-islet pro-inflammatory cytokines from fa/fa rats: IL-1β, IL-6 and TNFα expressions were increased; IL-1R1 was also over-expressed with a cellular redistribution also observed for IL-6R. To get insight into the mechanisms involved in phenotypic alterations, abArrays were used to determine the expression profile of proteins implicated in different membrane receptors signaling, apoptosis and cell cycle pathways. Despite JNK overexpression, cell viability was unaffected probably because of decreases in cleaved caspase3 as well as in SMAC/DIABLO and APP, involved in the induction and amplification of apoptosis. Concerning β-cell proliferation, decreases in important cell cycle regulators (Cyclin D1, p35) and increased expression of SMAD4 probably contribute to counteract and restrain hyperplasia in fa/fa rat islets. Finally and probably as a result of IL-1β and IL-1R1 increased expressions with sub-cellular redistribution of the receptor, islets from fa/fa rats were found more sensitive to both stimulating and inhibitory concentrations of the cytokine; this confers some physiopathological relevance to a possible autocrine regulation of β-cell function by IL-1β. These results support the hypothesis that pancreatic islets from prediabetic fa/fa rats undergo an inflammatory process. That the latter could contribute to β-cell hyperactivity/proliferation and possibly lead to progressive β-cell failure in these animals, deserves further investigations.
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spelling pubmed-31496182011-08-08 Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets Chentouf, Myriam Dubois, Gregor Jahannaut, Céline Castex, Françoise Lajoix, Anne Dominique Gross, René Peraldi-Roux, Sylvie PLoS One Research Article Inappropriate food intake-related obesity and more importantly, visceral adiposity, are major risk factors for the onset of type 2 diabetes. Evidence is emerging that nutriment-induced β-cell dysfunction could be related to indirect induction of a state of low grade inflammation. Our aim was to study whether hyperphagia associated obesity could promote an inflammatory response in pancreatic islets leading to ß-cell dysfunction. In the hyperphagic obese insulin resistant male Zucker rat, we measured the level of circulating pro-inflammatory cytokines and estimated their production as well as the expression of their receptors in pancreatic tissue and β-cells. Our main findings concern intra-islet pro-inflammatory cytokines from fa/fa rats: IL-1β, IL-6 and TNFα expressions were increased; IL-1R1 was also over-expressed with a cellular redistribution also observed for IL-6R. To get insight into the mechanisms involved in phenotypic alterations, abArrays were used to determine the expression profile of proteins implicated in different membrane receptors signaling, apoptosis and cell cycle pathways. Despite JNK overexpression, cell viability was unaffected probably because of decreases in cleaved caspase3 as well as in SMAC/DIABLO and APP, involved in the induction and amplification of apoptosis. Concerning β-cell proliferation, decreases in important cell cycle regulators (Cyclin D1, p35) and increased expression of SMAD4 probably contribute to counteract and restrain hyperplasia in fa/fa rat islets. Finally and probably as a result of IL-1β and IL-1R1 increased expressions with sub-cellular redistribution of the receptor, islets from fa/fa rats were found more sensitive to both stimulating and inhibitory concentrations of the cytokine; this confers some physiopathological relevance to a possible autocrine regulation of β-cell function by IL-1β. These results support the hypothesis that pancreatic islets from prediabetic fa/fa rats undergo an inflammatory process. That the latter could contribute to β-cell hyperactivity/proliferation and possibly lead to progressive β-cell failure in these animals, deserves further investigations. Public Library of Science 2011-08-03 /pmc/articles/PMC3149618/ /pubmed/21826222 http://dx.doi.org/10.1371/journal.pone.0022954 Text en Chentouf et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chentouf, Myriam
Dubois, Gregor
Jahannaut, Céline
Castex, Françoise
Lajoix, Anne Dominique
Gross, René
Peraldi-Roux, Sylvie
Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets
title Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets
title_full Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets
title_fullStr Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets
title_full_unstemmed Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets
title_short Excessive Food Intake, Obesity and Inflammation Process in Zucker fa/fa Rat Pancreatic Islets
title_sort excessive food intake, obesity and inflammation process in zucker fa/fa rat pancreatic islets
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3149618/
https://www.ncbi.nlm.nih.gov/pubmed/21826222
http://dx.doi.org/10.1371/journal.pone.0022954
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