Title: In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion
Authors: Chimienti, Fabrice ×
Devergnas, Séverine
Pattou, François
Schuit, Frans
Garcia-Cuenca, Rachel
Vandewalle, Brigitte
Kerr-Conte, Julie
Van Lommel, Leentje
Grunwald, Didier
Favier, Alain
Seve, Michel #
Issue Date: Oct-2006
Series Title: Journal of Cell Science vol:119 issue:20 pages:4199-4206
Abstract: 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.
ISSN: 0021-9533
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gene Expression Unit
Biochemistry Section (Medicine) (-)
× corresponding author
# (joint) last author

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