Zinc transporter gene expression is regulated by pro-inflammatory cytokines: a potential role for zinc transporters in beta-cell apoptosis?

Laerke Egefjord, Jens Ledet Jensen, Claus Heiner Bang-Berthelsen, Andreas Bronden Petersen, Kamille Smidt, Ole Schmitz, Allan Ertman Karlsen, Flemming Pociot, Fabrice Chimienti, Jorgen Rungby, Nils E. Magnusson

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Background: beta-cells are extremely rich in zinc and zinc homeostasis is regulated by zinc transporter proteins. beta-cells are sensitive to cytokines, interleukin-1 beta (IL-1 beta) has been associated with beta-cell dysfunction and -death in both type 1 and type 2 diabetes. This study explores the regulation of zinc transporters following cytokine exposure.Methods: The effects of cytokines IL-1 beta, interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) on zinc transporter gene expression were measured in INS-1-cells and rat pancreatic islets. Being the more sensitive transporter, we further explored ZnT8 (Slc30A8): the effect of ZnT8 over expression on cytokine induced apoptosis was investigated as well as expression of the insulin gene and two apoptosis associated genes, BAX and BCL2.Results: Our results showed a dynamic response of genes responsible for beta-cell zinc homeostasis to cytokines: IL-1 beta down regulated a number of zinc-transporters, most strikingly ZnT8 in both islets and INS-1 cells. The effect was even more pronounced when mixing the cytokines. TNF-alpha had little effect on zinc transporter expression. IFN-gamma down regulated a number of zinc transporters. Insulin expression was down regulated by all cytokines. ZnT8 over expressing cells were more sensitive to IL-1 beta induced apoptosis whereas no differences were observed with IFN gamma, TNF-alpha, or a mixture of cytokines.Conclusion: The zinc transporting system in beta-cells is influenced by the exposure to cytokines. Particularly ZnT8, which has been associated with the development of diabetes, seems to be cytokine sensitive.
Original languageEnglish
JournalBmc Endocrine Disorders
Issue number1
Number of pages7
Publication statusPublished - 2009
Externally publishedYes


  • Endocrinology, Diabetes and Metabolism
  • gamma interferon
  • insulin
  • interleukin 1beta
  • protein Bax
  • protein bcl 2
  • tumor necrosis factor alpha
  • zinc transporter
  • animal cell
  • apoptosis
  • article
  • controlled study
  • down regulation
  • gene expression
  • nonhuman
  • nucleotide sequence
  • pancreas islet beta cell
  • protein expression
  • protein function
  • protein transport
  • rat
  • sensitivity analysis
  • Internal medicine
  • RC31-1245
  • Medicine

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