Zinc transporter 8

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 21.12.2021

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Synonym(s)

Zinc transporter 8; ZnT-8

Definition
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Intracellular zinc homeostasis is regulated by zinc-binding proteins and zinc transporters (Rink et al. 2007). The zinc transporters are encoded by two SLC ("solute linked carrier") gene families:

  • SLC39 family members (Zip, "Zrt- and Irt-like proteins") increase cytoplasmic zinc levels by zinc uptake.
  • Members of the SLC30 family (ZnT, zinc transporter/exporter; CDF family, "cation diffusion facilitator") decrease intracellular zinc concentration by transporting zinc out of the cell or into vesicular structures.

To date, 15 Zips and 9 ZnTs have been detected in various, human cells.

The zinc transporter 8, ZnT-8 is a pancreas-specific zinc transporter expressed in pancreatic beta cells. ZnT 8 is a transmembrane protein of the secretory vesicles of beta cells and belongs to the SLC30 family.

ZnT8 is encoded by the gene SLC30A8 (Solute carrier family 30, member 8). There is an association between ZnT8 polymorphisms and type 2 diabetes. For ZnT-8, no expression has yet been shown in peripheral blood mononuclear cells (PBMC). In pancreatic beta cells, it mediates the transport of cytoplasmic zinc into intracellular vesicles, where it is required for the maturation and storage of insulin(Chimienti et al 2005).

General information
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The antibody against the zinc transporter 8 (anti-ZnT8-Ak) is a new marker in the prognosis and diagnosis of type 1 diabetes. The detection of this antibody indicates a high risk of diabetes. ZnT8 antibodies are detected in 80% of newly diagnosed type 1 diabetics, while controls showed 2%, type 2 diabetics <3%, patients with other autoimmune diseases up to 20% ZnT8 antibodies.

Literature
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  1. Chausmer AB (1998) Zinc, insulin and diabetes. J Am Coll Nutr 17: 109-115.
  2. Chimienti F et al (2005) ZnT-8, a pancreatic beta-cell-specific zinc transporter. Biometals 18: 313-317.
  3. Fraker PJ et al (1997) A reappraisal of the role of zinc in life and death decisions of cells. Proc. Soc. Exp Biol Med 215: 229-236.
  4. Fraker PJ et al (2004) Reprogramming of the immune system during zinc deficiency. Annu Rev Nutr 24: 277-298.
  5. Iguchi K et al (2002) High-level expression of zinc transporter-2 in the rat lateral and dorsal prostate. J Androl 23: 819-824.
  6. Inoue K et al (2002) Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5. Human Mol Genet 11: 1775-1784.
  7. Kambe T et al (2004) Overview of mammalian zinc transporters. Cell Mol Life Sci 61: 49-68.
  8. Overbeck S (2008) The regulation of zinc transporters and their influence on intracellular zinc homeostasis in leukocytes. Dissertation. Publication server of RWTH Aachen University
  9. Rink L et al (2001) Extracellular and immunological actions of zinc. Biometals 14: 367-383.
  10. Rink L et al (2007) Zinc homeostasis and immunity. Trends Immunol 28: 1-4.

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Last updated on: 21.12.2021