PMID: identifiant
de la référence Pubmed : |
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 (16984975) |
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| titre : |
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In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion. |
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| auteur(s) : |
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Fabrice Chimienti ( ) 1, 2, Séverine Devergnas2, François Pattou3, Frans Schuit4, Rachel Garcia-Cuenca1, Brigitte Vandewalle3, Julie Kerr-Conte3, Leentje Van Lommel4, Didier Grunwald5, Alain Favier2, Michel Seve2 |
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| laboratoire : |
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| 1 : |
MELLITECH SAS |
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| Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA) - Grenoble – Institut Nanosciences et Cryogénie (INAC) – Service de Chimie Inorganique et Biologique (SCIB) |
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| Bâtiment C5 - 38054 Grenoble |
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| France |
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| 2 : |
SCIB - Service de Chimie Inorganique et Biologique |
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| Institut Nanosciences et Cryogénie (INAC) – CEA : UMR E3 – CNRS : FRE3200 – Université Joseph Fourier - Grenoble I |
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| Département de Recherche Fondamentale sur la Matière Condensée (DRFMC) - 17 rue des Martyrs, 38054 Grenoble Cedex 9 |
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| France |
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| 3 : |
Therapie Cellulaire du Diabete |
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| http://www.univ-lille2.fr/ilots/ |
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| INSERM : ERM106 – Université Lille II - Droit et santé |
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| Faculte de Medecine LILLE 1, Place de Verdun 59045 LILLE CEDEX |
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| France |
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| 4 : |
Gene Expression Unit |
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| Katholieke Universiteit Leuven |
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| Division of Biochemistry - 3000 Leuven |
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| France |
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| 5 : |
Laboratoire Canaux Ioniques et Signalisation |
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| Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA) - Grenoble – Département Réponse et Dynamique Cellulaire (DRDC) – Laboratoire des composants imprimés (LCI) |
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| 17 rue des Martyrs 38054 Grenoble Cedex 9 |
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| France |
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| Équipe de recherche : |
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ANTE-INSERM U836, équipe 4, Muscles et pathologies |
| résumé : |
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Insulin-secreting pancreatic beta cells are exceptionally rich in zinc. In these cells, zinc is required for zinc-insulin crystallization within secretory vesicles. Secreted zinc has also been proposed to be a paracrine and autocrine modulator of glucagon and insulin secretion in pancreatic alpha and beta cells, respectively. However, little is known about the molecular mechanisms underlying zinc accumulation in insulin-containing vesicles. We previously identified a pancreas-specific zinc transporter, ZnT-8, which colocalized with insulin in cultured beta cells. In this paper we studied its localization in human pancreatic islet cells, and its effect on cellular zinc content and insulin secretion. In human pancreatic islet cells, ZnT-8 was exclusively expressed in insulin-producing beta cells, and colocalized with insulin in these cells. ZnT-8 overexpression stimulated zinc accumulation and increased total intracellular zinc in insulin-secreting INS-1E cells. Furthermore, ZnT-8-overexpressing cells display enhanced glucose-stimulated insulin secretion compared with control cells, only for a high glucose challenge, i.e. >10 mM glucose. Altogether, these data strongly suggest that the zinc transporter ZnT-8 is a key protein for both zinc accumulation and regulation of insulin secretion in pancreatic beta cells. |
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| domaine : |
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Sciences du Vivant/Cancérologie
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langue du texte
intégral : |
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Anglais |
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| ISSN : |
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0021-9533 |
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| type de publication : |
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Articles dans des revues avec comité de lecture |
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| DOI : |
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10.1242/jcs.03164 |
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| journal : |
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| Journal of Cell Science (J Cell Sci) |
| Publisher |
Company of Biologists |
| ISSN |
0021-9533 (eISSN : 1477-9137) |
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| Audience : |
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internationale |
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| date de publication : |
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15/10/2006 |
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date de publication
électronique : |
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19/09/2006 |
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| volume : |
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119 |
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| numéro : |
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Pt 20 |
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| page, identifiant, ... : |
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4199-206 |
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| mots-clés auteur : |
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Langerhans islets – Beta cell – Insulin – Insulin secretion – Zinc transport – Zinc |
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| Descripteur(s) MeSH : |
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Animals – Biological Transport – Cation Transport Proteins – Cell Line – Cell Membrane – Cell Survival – Dose-Response Relationship – Drug – Gene Expression – Glucagon – Glucose – Green Fluorescent Proteins – Hela Cells – Humans – Insulin – Insulin-Secreting Cells – Islets of Langerhans – Male – Mice – Microscopy – Confocal – Fluorescence – Models – Biological – Recombinant Fusion Proteins – Secretory Vesicles – Zinc |
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| contrat, financement : |
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This work was supported by a grant from the Programme de Toxicologie Nucléaire Environnementale (www.toxnuc-e.org) to M.S. and a grant from Centre Evian pour l'Eau to F.C. |
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