title: Islet Brain 1 Protects Insulin Producing Cells against Lipotoxicity.
abstract: 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.
authors.affiliation: Service of Internal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland ; University of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, France.
authors.forename: Saška
authors.initials: S
authors.lastname: Brajkovic
authors.affiliation: Service of Internal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland ; University of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, France ; Department of Pharmacology and the Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada.
authors.forename: Mourad
authors.initials: M
authors.lastname: Ferdaoussi
authors.affiliation: University of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, France ; University of Lille, EGID FR 3508, Department of Endocrine Surgery, Lille University Hospital, UMR INSERM 1190, Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Pawlowski
authors.affiliation: University of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Ezanno
authors.affiliation: University of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Plaisance
authors.affiliation: Department of Molecular and Cellular Biochemistry, Ohio State University, 1060 Carmack Road, Columbus, OH, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Zmuda
authors.affiliation: Department of Molecular and Cellular Biochemistry, Ohio State University, 1060 Carmack Road, Columbus, OH, USA.
authors.forename: Tsonwin
authors.initials: T
authors.lastname: Hai
authors.affiliation: University of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, France.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Annicotte
authors.affiliation: Service of Internal Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Gérard
authors.initials: G
authors.lastname: Waeber
authors.affiliation: University of Lille, European Genomic Institute for Diabetes (EGID) FR 3508, UMR CNRS 8199, Faculty of Medicine West, 1 place de Verdun, 59045 Lille, France.
authors.forename: Amar
authors.initials: A
authors.lastname: Abderrahmani
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000235:genetics; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019308:Palmitic Acid / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007328:Insulin; C110528:Mapk8ip1 protein, rat; D012333:RNA, Messenger; D019308:Palmitic Acid