Zinc Fluxes during Acute and Chronic Exposure of INS-1E Cells to Increasing Glucose Levels

L. G. Søndergaard; B. Brock; M. Stoltenberg; A. Flyvbjerg; O. Schmitz; K. Smidt; G. Danscher; J. Rungby

doi:10.1055/s-2005-861290

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2005; 37(3): 133-139
DOI: 10.1055/s-2005-861290

Original Basic

Zinc Fluxes during Acute and Chronic Exposure of INS-1E Cells to Increasing Glucose Levels

L. G. Søndergaard¹ , B. Brock² , M. Stoltenberg¹ , A. Flyvbjerg³ , O. Schmitz^2, ³ , K. Smidt² , G. Danscher¹ , J. Rungby^2, ⁴

¹Institute of Anatomy, University of Aarhus
²Department of Clinical Pharmacology, University of Aarhus
³Medical Department M, Aarhus University Hospital, Denmark
⁴Medical Department C, Aarhus University Hospital, Denmark

Abstract

Zinc in beta-cell secretory vesicles is essential for insulin hexamerization, and tight vesicular zinc regulation is mandatory. Little is known about zinc ion fluxes across the secretory vesicle membrane and the influence of changes in the extracellular environment on vesicular zinc. Our study aim was to investigate the effect of acute and chronic exposure to various glucose concentrations on zinc in secretory vesicles, the relation between zinc and insulin, and the presence of two zinc transporters, ZnT1 and ZnT4, in INS-1E cells. Zinc ions were demonstrated and semi-quantified using zinc-sulfide autometallography. Insulin content and secreted insulin were measured. Measurements were made on INS-1E cells after exposure to 2.0, 6.6, 16.7, and 24.6 mmol/l glucose for 1, 24, and 96 hours. 1h: Increasing glucose resulted in no changes in intravesicular zinc ions at 2, and 24.6 mmol/l glucose, but a slight increase at 16.7 mmol/l glucose. 24 and 96 h: Increasing glucose led to decreased vesicular zinc ion content accompanied by a decrease in insulin content. ZnT1 and ZnT4 were present in the cytoplasm. Our results demonstrate that intra-vesicular zinc ions respond to changes in the extra-cellolar glucose concentration, especially during chronic high glucose concentrations, where the content of vesicular zinc ions decreases.

Key words

Insulin - Secretory vesicles - Zinc transporters - Autometallography - ZnT

Full Text

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Liselotte G. Søndergaard

Institute of Anatomy, University of Aarhus

8000 Aarhus C · Denmark ·

Phone: +45(8942)3027

Fax: +45(8942)3060

Email: lgs@neuro.au.dk