Title: Insulin crystallisation depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice
Authors: Lemaire, Katleen ×
Ravier, M.A
Schraenen, Anica
Creemers, John
Van de Plas, Raf
Granvik, Mikaela
Van Lommel, Leentje
Waelkens, Etienne
Chimienti, F
Rutter, G.A
Gilon, P
in't Veld, P.A
Schuit, Frans #
Issue Date: Sep-2009
Publisher: National Academy of Sciences
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:106 issue:35 pages:14872-14877
Abstract: Zinc co-crystallizes with insulin in dense core secretory granules, but its role in insulin biosynthesis, storage and secretion is unknown. In this study we assessed the role of the zinc transporter ZnT8 using ZnT8-knockout (ZnT8(-/-)) mice. Absence of ZnT8 expression caused loss of zinc release upon stimulation of exocytosis, but normal rates of insulin biosynthesis, normal insulin content and preserved glucose-induced insulin release. Ultrastructurally, mature dense core insulin granules were rare in ZnT8(-/-) beta cells and were replaced by immature, pale insulin "progranules," which were larger than in ZnT8(+/+) islets. When mice were fed a control diet, glucose tolerance and insulin sensitivity were normal. However, after high-fat diet feeding, the ZnT8(-/-) mice became glucose intolerant or diabetic, and islets became less responsive to glucose. Our data show that the ZnT8 transporter is essential for the formation of insulin crystals in beta cells, contributing to the packaging efficiency of stored insulin. Interaction between the ZnT8(-/-) genotype and diet to induce diabetes is a model for further studies of the mechanism of disease of human ZNT8 gene mutations.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gene Expression Unit
Laboratory of Protein Phosphorylation and Proteomics
ESAT - STADIUS, Stadius Centre for Dynamical Systems, Signal Processing and Data Analytics
Department of Human Genetics - miscellaneous
Laboratory of Phosphoproteomics (-)
× corresponding author
# (joint) last author

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