Effects of zinc supplementation and zinc chelation on in vitro β-cell function in INS-1E cells

BMC Research Notes

Kamille Smidt¹  Jørgen Rungby¹  Astrid Knuhtsen¹  Agnete Larsen¹  Sanne Bjørn Nygaard¹ 

[1] Department of Biomedicine, Centre of Pharmacology and Pharmacotherapy, Health, Aarhus University, Wilhelm Meyers Allé 4, Bld 1240, Aarhus, 8000, Denmark

关键词: Diabetes;    β –cell;    INS-1E cells;    TPEN;    Chelation;    Metallothionein;    Zinc transporter;    Insulin;    Zinc;   

Others  :  1134499
DOI  :  10.1186/1756-0500-7-84

 received in 2013-04-11, accepted in 2014-02-04,  发布年份 2014

【 摘 要 】

Background

Zinc is essential for the activities of pancreatic β-cells, especially insulin storage and secretion. Insulin secretion leads to co-release of zinc which contributes to the paracrine communication in the pancreatic islets. Zinc-transporting proteins (zinc-regulated transporter, iron-regulated transporter-like proteins [ZIPs] and zinc transporters [ZnTs]) and metal-buffering proteins (metallothioneins, MTs) tightly regulate intracellular zinc homeostasis. The present study investigated how modulation of cellular zinc availability affects β-cell function using INS-1E cells.

Results

Using INS-1E cells, we found that zinc supplementation and zinc chelation had significant effects on insulin content and insulin secretion. Supplemental zinc within the physiological concentration range induced insulin secretion. Insulin content was reduced by zinc chelation with N,N,N’,N-tektrakis(2-pyridylmethyl)-ethylenediamine. The changes in intracellular insulin content following exposure to various concentrations of zinc were reflected by changes in the expression patterns of MT-1A, ZnT-8, ZnT-5, and ZnT-3. Furthermore, high zinc concentrations induced cell necrosis while zinc chelation induced apoptosis. Finally, cell proliferation was sensitive to changes in zinc the concentration.

Conclusion

These results indicate that the β-cell-like function and survival of INS-1E cells are dependent on the surrounding zinc concentrations. Our results suggest that regulation of zinc homeostasis could represent a pharmacological target.

【 授权许可】

   
2014 Nygaard et al.; licensee BioMed Central Ltd.

【 图 表 】

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