Titre
The gene MAPK8IP1, encoding islet-brain-1, is a candidate for type 2 diabetes.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Waeber, G.
Auteure/Auteur
Delplanque, J.
Auteure/Auteur
Bonny, C.
Auteure/Auteur
Mooser, V.
Auteure/Auteur
Steinmann, M.
Auteure/Auteur
Widmann, C.
Auteure/Auteur
Maillard, A.
Auteure/Auteur
Miklossy, J.
Auteure/Auteur
Dina, C.
Auteure/Auteur
Hani, E.H.
Auteure/Auteur
Vionnet, N.
Auteure/Auteur
Nicod, P.
Auteure/Auteur
Boutin, P.
Auteure/Auteur
Froguel, P.
Auteure/Auteur
Liens vers les personnes
ISSN
1061-4036
Statut éditorial
Publié
Date de publication
2000
Volume
24
Numéro
3
Première page
291
Dernière page/numéro d’article
5
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
Type 2 diabetes is a polygenic and genetically heterogeneous disease . The age of onset of the disease is usually late and environmental factors may be required to induce the complete diabetic phenotype. Susceptibility genes for diabetes have not yet been identified. Islet-brain-1 (IB1, encoded by MAPK8IP1), a novel DNA-binding transactivator of the glucose transporter GLUT2 (encoded by SLC2A2), is the homologue of the c-Jun amino-terminal kinase-interacting protein-1 (JIP-1; refs 2-5). We evaluated the role of IBi in beta-cells by expression of a MAPK8IP1 antisense RNA in a stable insulinoma beta-cell line. A 38% decrease in IB1 protein content resulted in a 49% and a 41% reduction in SLC2A2 and INS (encoding insulin) mRNA expression, respectively. In addition, we detected MAPK8IP1 transcripts and IBi protein in human pancreatic islets. These data establish MAPK8IP1 as a candidate gene for human diabetes. Sibpair analyses performed on i49 multiplex French families with type 2 diabetes excluded MAPK8IP1 as a major diabetogenic locus. We did, however, identify in one family a missense mutation located in the coding region of MAPK8IP1 (559N) that segregated with diabetes. In vitro, this mutation was associated with an inability of IB1 to prevent apoptosis induced by MAPK/ERK kinase kinase 1 (MEKK1) and a reduced ability to counteract the inhibitory action of the activated c-JUN amino-terminal kinase (JNK) pathway on INS transcriptional activity. Identification of this novel non-maturity onset diabetes of the young (MODY) form of diabetes demonstrates that IB1 is a key regulator of 3-cell function.
Sujets
PID Serval
serval:BIB_82C758FFFC94
PMID
Date de création
2008-11-17T07:57:48.035Z
Date de création dans IRIS
2025-05-21T01:06:54Z