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- Title
The Long-Acting GLP-1 Analogue Liraglutide Regulates Zinc Transporter mRNA in β-Cells.
- Authors
Rungby, Jorgen; Wogensen, Lise; Brock, Birgitte; Schmitz, Ole; Jeppesen, Johanne B.; Knudsen, Lotte Bjerre; Smidt, Kamille
- Abstract
Background: Zink transporters (ZnT)-proteins regulate zinc flux into β-cell vesicles. β-cells depend on zinc for crystallization of insulin. Zinc efflux, which is also regulated by ZnTs controls β-cell mass and glucagon secretion. We examined whether glucose levels, zinc depletion, GLP-1 or liraglutide affect ZnT mRNA expression. Methods: The rat beta-cell line INSI-E was exposed to 2, 5 or 16 mM glucose for 24 hrs. For zinc depletion the INS1-E cells were exposed to 100 µM DEDTC for 24 hrs. GLP-I and liraglutide was added at 5 or 16 nM glucose (GLP-I 1 or 10 nM; liraglutide 10 or 100 nM) for 24 hrs. ZnT mRNA was measured by RT-PCR Insulin was measured by Elisa. Results: Relative to 5 mM glucose, 2 mM glucose caused a down-regulation of ZnT-3 and an up-regulation of most other ZnT mRNA. 16 mM caused ZnT3 up-regulation and down-regulation of other ZnT mRNA. Results were significant for ZnT3, ZnT5 and ZnT8, all transporters with high expression levels in β-cells. Zinc chelation lowered insulin expression and content and - non-significantly -- insulin secretion along with a ZnT3 up-regulation. Liraglutide augmented glucose stimulated ZnT3 expression (1.73 fold increase), stimulated insulin expression and eliminated the glucose dependant down-regulation of ZnT7 and ZnT8. This study demonstrates that ZnT mRNA in β-cells responds to changes in glucose and zinc, supporting the hypothesis that ZnTs participate in insulin processing and that zinc trafficking in β-cells is regulated. Furthermore, longterm (liraglutide) but not short-term (GLP-1) stimulation of the GLP-I receptor has significant influences on ZnT mRNA expression indicating that this system is a potential target for pharmacological manipulation.
- Subjects
GLUCAGON-like peptide 1; REGULATION of biological transport; ZINC in the body; MESSENGER RNA; PANCREATIC beta cells; INSULIN
- Publication
Diabetes, 2007, Vol 56, pA437
- ISSN
0012-1797
- Publication type
Article