title: JNK3 is required for the cytoprotective effect of exendin 4.
abstract: Preservation of beta cell against apoptosis is one of the therapeutic benefits of the glucagon-like peptide-1 (GLP1) antidiabetic mimetics for preserving the functional beta cell mass exposed to diabetogenic condition including proinflammatory cytokines. The mitogen activated protein kinase 10 also called c-jun amino-terminal kinase 3 (JNK3) plays a protective role in insulin-secreting cells against death caused by cytokines. In this study, we investigated whether the JNK3 expression is associated with the protective effect elicited by the GLP1 mimetic exendin 4. We found an increase in the abundance of JNK3 in isolated human islets and INS-1E cells cultured with exendin 4. Induction of JNK3 by exendin 4 was associated with an increased survival of INS-1E cells. Silencing of JNK3 prevented the cytoprotective effect of exendin 4 against apoptosis elicited by culture condition and cytokines. These results emphasize the requirement of JNK3 in the antiapoptotic effects of exendin 4.
authors.affiliation: Lille 2 University, University of Lille Nord de France, European Genomic Institute for Diabetes, EGID FR 3508, UMR 8199, Lille, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Ezanno
authors.affiliation: Lille 2 University, University of Lille Nord de France, European Genomic Institute for Diabetes, EGID FR 3508, UMR 8199, Lille, France ; Department of Endocrine Surgery, Lille 2 University, University of Lille Nord de France, Lille University Hospital, INSERM UMR 859, Biotherapies for Diabetes, European Genomic Institute for Diabetes, Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Pawlowski
authors.affiliation: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Saida
authors.initials: S
authors.lastname: Abdelli
authors.affiliation: Lille 2 University, University of Lille Nord de France, European Genomic Institute for Diabetes, EGID FR 3508, UMR 8199, Lille, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Boutry
authors.affiliation: Department of Endocrine Surgery, Lille 2 University, University of Lille Nord de France, Lille University Hospital, INSERM UMR 859, Biotherapies for Diabetes, European Genomic Institute for Diabetes, Lille, France.
authors.forename: Valery
authors.initials: V
authors.lastname: Gmyr
authors.affiliation: Department of Endocrine Surgery, Lille 2 University, University of Lille Nord de France, Lille University Hospital, INSERM UMR 859, Biotherapies for Diabetes, European Genomic Institute for Diabetes, Lille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Kerr-Conte
authors.affiliation: Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois (CHUV), University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bonny
authors.affiliation: Department of Endocrine Surgery, Lille 2 University, University of Lille Nord de France, Lille University Hospital, INSERM UMR 859, Biotherapies for Diabetes, European Genomic Institute for Diabetes, Lille, France.
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.affiliation: Lille 2 University, University of Lille Nord de France, European Genomic Institute for Diabetes, EGID FR 3508, UMR 8199, Lille, France ; Department of Endocrine Surgery, Lille 2 University, University of Lille Nord de France, Lille University Hospital, INSERM UMR 859, Biotherapies for Diabetes, European Genomic Institute for Diabetes, Lille, France.
authors.forename: Amar
authors.identifier: 0000-0003-0752-0343
authors.initials: A
authors.lastname: Abderrahmani
mesh_terms: D000818:Animals; D017209:Apoptosis; D000077270:Exenatide; D020868:Gene Silencing; D052216:Glucagon-Like Peptide 1 / Q000737:chemistry*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry; D007249:Inflammation; D007328:Insulin / Q000737:chemistry; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D014688:Venoms / Q000737:chemistry*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010455:Peptides; D034741:RNA, Small Interfering; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D048057:Mitogen-Activated Protein Kinase 10