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In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion.
Chimienti F., Devergnas S., Pattou F., Schuit F. C., Garcia-Cuenca R., Vandewalle B., Kerr-Conte J., Van Lommel L., Grunwald D., Favier A. et al
Journal of Cell Science 119, Pt 20 (2006) 4199-206 - http://www.hal.inserm.fr/inserm-00176696
(16984975)
In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion.
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
1 :  MELLITECH SAS
Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA) - Grenoble – Institut Nanosciences et Cryogénie (INAC) – Service de Chimie Inorganique et Biologique (SCIB)
Bâtiment C5 - 38054 Grenoble
France
2 :  SCIB - UMR E3 - Service de Chimie Inorganique et Biologique
http://inac.cea.fr/scib/Phocea/Vie_des_labos/Ast/ast_service.php?id_unit=542
Université Joseph Fourier - Grenoble I – CEA : DSM/INAC – CNRS : FRE3200
SCIB UMR E3, Institut Nanosciences et Cryogénie, CEA/Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9
France
3 :  Therapie Cellulaire du Diabete
http://www.univ-lille2.fr/ilots/
INSERM : ERM106 – Université Lille II - Droit et santé
Faculte de Medecine LILLE 1, Place de Verdun 59045 LILLE CEDEX
France
4 :  Gene Expression Unit
Katholieke Universiteit Leuven
Division of Biochemistry - 3000 Leuven
France
5 :  Laboratoire Canaux Ioniques et Signalisation
Commissariat à l'Énergie Atomique et aux Énergies Alternatives (CEA) - Grenoble – Département Réponse et Dynamique Cellulaire (DRDC) – Laboratoire des composants imprimés (LCI)
17 rue des Martyrs 38054 Grenoble Cedex 9
France
ANTE-INSERM U836, équipe 4, Muscles et pathologies
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.
Sciences du Vivant/Cancérologie
Anglais
0021-9533

Articles dans des revues avec comité de lecture
10.1242/jcs.03164
Journal of Cell Science (J Cell Sci)
Publisher Company of Biologists
ISSN 0021-9533 (eISSN : 1477-9137)
internationale
15/10/2006
19/09/2006
119
Pt 20
4199-206

Langerhans islets – Beta cell – Insulin – Insulin secretion – Zinc transport – Zinc
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
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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