Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity

Chronic intake of saturated free fatty acids is associated with diabetes and may contribute to the impairment of functional beta cell mass. Mitogen activated protein kinase 8 interacting protein 1 also called islet brain 1 (IB1) is a candidate gene for diabetes that is required for beta cell surviva...

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Main Authors: Saška Brajkovic, Mourad Ferdaoussi, Valérie Pawlowski, Hélène Ezanno, Valérie Plaisance, Erik Zmuda, Tsonwin Hai, Jean-Sébastien Annicotte, Gérard Waeber, Amar Abderrahmani
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2016/9158562
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author Saška Brajkovic
Mourad Ferdaoussi
Valérie Pawlowski
Hélène Ezanno
Valérie Plaisance
Erik Zmuda
Tsonwin Hai
Jean-Sébastien Annicotte
Gérard Waeber
Amar Abderrahmani
author_facet Saška Brajkovic
Mourad Ferdaoussi
Valérie Pawlowski
Hélène Ezanno
Valérie Plaisance
Erik Zmuda
Tsonwin Hai
Jean-Sébastien Annicotte
Gérard Waeber
Amar Abderrahmani
author_sort Saška Brajkovic
collection DOAJ
description Chronic intake of saturated free fatty acids is associated with diabetes and may contribute to the impairment of functional beta cell mass. Mitogen activated protein kinase 8 interacting protein 1 also called islet brain 1 (IB1) is a candidate gene for diabetes that is required for beta cell survival and glucose-induced insulin secretion (GSIS). In this study we investigated whether IB1 expression is required for preserving beta cell survival and function in response to palmitate. Chronic exposure of MIN6 and isolated rat islets cells to palmitate led to reduction of the IB1 mRNA and protein content. Diminution of IB1 mRNA and protein level relied on the inducible cAMP early repressor activity and proteasome-mediated degradation, respectively. Suppression of IB1 level mimicked the harmful effects of palmitate on the beta cell survival and GSIS. Conversely, ectopic expression of IB1 counteracted the deleterious effects of palmitate on the beta cell survival and insulin secretion. These findings highlight the importance in preserving the IB1 content for protecting beta cell against lipotoxicity in diabetes.
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publishDate 2016-01-01
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series Journal of Diabetes Research
spelling doaj-art-d2d61d7052cd4e23b7a7b55d79d476fa2025-08-20T02:19:51ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/91585629158562Islet Brain 1 Protects Insulin Producing Cells against LipotoxicitySaška Brajkovic0Mourad Ferdaoussi1Valérie Pawlowski2Hélène Ezanno3Valérie Plaisance4Erik Zmuda5Tsonwin Hai6Jean-Sébastien Annicotte7Gérard Waeber8Amar Abderrahmani9Service of Internal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, SwitzerlandService of Internal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, SwitzerlandUniversity of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, FranceUniversity of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, FranceUniversity of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, FranceDepartment of Molecular and Cellular Biochemistry, Ohio State University, 1060 Carmack Road, Columbus, OH, USADepartment of Molecular and Cellular Biochemistry, Ohio State University, 1060 Carmack Road, Columbus, OH, USAUniversity of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, FranceService of Internal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, SwitzerlandUniversity of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, FranceChronic intake of saturated free fatty acids is associated with diabetes and may contribute to the impairment of functional beta cell mass. Mitogen activated protein kinase 8 interacting protein 1 also called islet brain 1 (IB1) is a candidate gene for diabetes that is required for beta cell survival and glucose-induced insulin secretion (GSIS). In this study we investigated whether IB1 expression is required for preserving beta cell survival and function in response to palmitate. Chronic exposure of MIN6 and isolated rat islets cells to palmitate led to reduction of the IB1 mRNA and protein content. Diminution of IB1 mRNA and protein level relied on the inducible cAMP early repressor activity and proteasome-mediated degradation, respectively. Suppression of IB1 level mimicked the harmful effects of palmitate on the beta cell survival and GSIS. Conversely, ectopic expression of IB1 counteracted the deleterious effects of palmitate on the beta cell survival and insulin secretion. These findings highlight the importance in preserving the IB1 content for protecting beta cell against lipotoxicity in diabetes.http://dx.doi.org/10.1155/2016/9158562
spellingShingle Saška Brajkovic
Mourad Ferdaoussi
Valérie Pawlowski
Hélène Ezanno
Valérie Plaisance
Erik Zmuda
Tsonwin Hai
Jean-Sébastien Annicotte
Gérard Waeber
Amar Abderrahmani
Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity
Journal of Diabetes Research
title Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity
title_full Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity
title_fullStr Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity
title_full_unstemmed Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity
title_short Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity
title_sort islet brain 1 protects insulin producing cells against lipotoxicity
url http://dx.doi.org/10.1155/2016/9158562
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AT tsonwinhai isletbrain1protectsinsulinproducingcellsagainstlipotoxicity
AT jeansebastienannicotte isletbrain1protectsinsulinproducingcellsagainstlipotoxicity
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AT amarabderrahmani isletbrain1protectsinsulinproducingcellsagainstlipotoxicity