Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Zinc Transport in the Pancreatic β-Cell: Roles of ZnT (SLC30A) and ZiP (SLC39A) Family Members

  • Elisa A. BellomoEmail author
  • Guy A. Rutter
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_499


 SLC30A;  SLC39A;  ZiP;  ZnT

Historical Background

Zinc is an essential component of many proteins and is crucial for several cellular functions such as cell mitosis, gene expression, and modulation of cellular receptors (Lichten and Cousins 2009). Failure to regulate zinc homeostasis thus leads to the development of a variety of pathologies, and mutations in several zinc transporter genes are linked to diseases in man. Hypozincemia is a condition where insufficient zinc is available for metabolic needs. It is usually the result of inadequate dietary intake of zinc but can also be associated with malabsorption. Diarrhea, acrodermatitis enteropathica, chronic liver and renal disease, diabetes and other chronic illnesses are all associated with zinc deficiency.

Increasing evidence suggests that changes in the expression or activity of specific zinc transporters might play a role in regulating the general zinc homeostasis. In this entry, the function of zinc transporters and...

This is a preview of subscription content, log in to check access.


  1. Bellomo EA, Meur G, et al. Glucose regulates free cytosolic Zn2+ concentration, Slc39 (ZiP), and metallothionein gene expression in primary pancreatic islet {beta}-cells. J Biol Chem. 2011;286(29):25778–89.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Chimienti F, Devergnas S, et al. In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion. J Cell Sci. 2006;119(Pt 20):4199–206.CrossRefPubMedGoogle Scholar
  3. Gyulkhandanyan AV, Lu H, et al. Investigation of transport mechanisms and regulation of intracellular Zn2+ in pancreatic alpha-cells. J Biol Chem. 2008;283(15):10184–97.CrossRefPubMedGoogle Scholar
  4. Huang X, Cuajungco MP, et al. Alzheimer’s disease, beta-amyloid protein and zinc. J Nutr. 2000;130(5S Suppl):1488S–92.CrossRefPubMedGoogle Scholar
  5. Hutton JC, Bailyes EM, et al. Biosynthesis and storage of insulin. Biochem Soc Trans. 1990;18(1):122–4.CrossRefPubMedGoogle Scholar
  6. Kambe T, Narita H, et al. Cloning and characterization of a novel mammalian zinc transporter, zinc transporter 5, abundantly expressed in pancreatic beta cells. J Biol Chem. 2002;277(21):19049–55.CrossRefPubMedGoogle Scholar
  7. Kanoni S, Nettleton JA, et al. Total zinc intake may modify the Glucose-Raising effect of a zinc transporter (SLC30A8) variant: a 14-cohort meta-analysis. Diabetes. 2011;60(9):2407–16. Epub 2011 Aug 1.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Li M, Zhang Y, et al. Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression. Proc Natl Acad Sci U S A. 2007;104(47):18636–41.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Lichten LA, Cousins RJ. Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev Nutr. 2009;29:153–76.CrossRefPubMedGoogle Scholar
  10. Nicolson TJ, Bellomo EA, et al. Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes-associated variants. Diabetes. 2009;58(9):2070–83.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Palmiter RD, Cole TB, et al. ZnT-3, a putative transporter of zinc into synaptic vesicles. Proc Natl Acad Sci U S A. 1996;93(25):14934–9.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Rutter GA. Think zinc: new roles for zinc in the control of insulin secretion. Islets. 2010;2(1):49–50.CrossRefPubMedGoogle Scholar
  13. Scott DA, Fisher AM. The insulin and the zinc content of normal and diabetic pancreas. J Clin Invest. 1938;17(6):725–8.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Seve M, Chimienti F, et al. In silico identification and expression of SLC30 family genes: an expressed sequence tag data mining strategy for the characterization of zinc transporters’ tissue expression. BMC Genomics. 2004;5(1):32.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Simons TJ. Calcium-dependent zinc efflux in human red blood cells. J Membr Biol. 1991;123(1):73–82.CrossRefPubMedGoogle Scholar
  16. Sladek R, Rocheleau G, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature. 2007;445(7130):881–5.CrossRefPubMedGoogle Scholar
  17. Smidt K, Jessen N, et al. SLC30A3 responds to glucose- and zinc variations in beta-cells and is critical for insulin production and in vivo glucose-metabolism during beta-cell stress. PLoS One. 2009;4(5):e5684.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Taylor KM, Nicholson RI. The LZT proteins; the LIV-1 subfamily of zinc transporters. Biochim Biophys Acta. 2003;1611(1–2):16–30.CrossRefPubMedGoogle Scholar
  19. Taylor KM, Morgan HE, et al. The emerging role of the LIV-1 subfamily of zinc transporters in breast cancer. Mol Med. 2007;13(7–8):396–406.PubMedPubMedCentralGoogle Scholar
  20. Vinkenborg JL, Nicolson TJ, et al. Genetically encoded FRET sensors to monitor intracellular Zn2+ homeostasis. Nat Methods. 2009;6(10):737–40.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Wang B, Schneider SN, et al. Enhanced cadmium-induced testicular necrosis and renal proximal tubule damage caused by gene-dose increase in a Slc39a8-transgenic mouse line. Am J Physiol Cell Physiol. 2007;292(4):C1523–35.CrossRefPubMedGoogle Scholar
  22. Wijesekara N, Chimienti F, et al. Zinc, a regulator of islet function and glucose homeostasis. Diabetes Obes Metab. 2009;11(Suppl 4):202–14.CrossRefPubMedGoogle Scholar
  23. Wijesekara N, Dai FF, et al. Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia. 2010;53(8):1656–68.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Williams NR, Rajput-Williams J, et al. Plasma, granulocyte and mononuclear cell copper and zinc in patients with diabetes mellitus. Analyst. 1995;120(3):887–90.CrossRefPubMedGoogle Scholar
  25. Zhang Y, Bharadwaj U, et al. ZIP4 regulates pancreatic cancer cell growth by activating IL-6/STAT3 pathway through zinc finger transcription factor CREB. Clin Cancer Res. 2010;16(5):1423–30.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Section of Cell Biology, Division of Diabetes, Endocrinology and Metabolism, Faculty of MedicineImperial College LondonSouth Kensington, LondonUK