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

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Encyclopedia of Signaling Molecules

Synonyms

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...

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References

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Huang X, Cuajungco MP, et al. Alzheimer’s disease, beta-amyloid protein and zinc. J Nutr. 2000;130(5S Suppl):1488S–92.

    Article  CAS  PubMed  Google Scholar 

  • Hutton JC, Bailyes EM, et al. Biosynthesis and storage of insulin. Biochem Soc Trans. 1990;18(1):122–4.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lichten LA, Cousins RJ. Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev Nutr. 2009;29:153–76.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Rutter GA. Think zinc: new roles for zinc in the control of insulin secretion. Islets. 2010;2(1):49–50.

    Article  PubMed  Google Scholar 

  • Scott DA, Fisher AM. The insulin and the zinc content of normal and diabetic pancreas. J Clin Invest. 1938;17(6):725–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  Google Scholar 

  • Simons TJ. Calcium-dependent zinc efflux in human red blood cells. J Membr Biol. 1991;123(1):73–82.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Taylor KM, Nicholson RI. The LZT proteins; the LIV-1 subfamily of zinc transporters. Biochim Biophys Acta. 2003;1611(1–2):16–30.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    PubMed  PubMed Central  CAS  Google Scholar 

  • Vinkenborg JL, Nicolson TJ, et al. Genetically encoded FRET sensors to monitor intracellular Zn2+ homeostasis. Nat Methods. 2009;6(10):737–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Wijesekara N, Chimienti F, et al. Zinc, a regulator of islet function and glucose homeostasis. Diabetes Obes Metab. 2009;11(Suppl 4):202–14.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Correspondence to Elisa A. Bellomo .

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Bellomo, E.A., Rutter, G.A. (2018). Zinc Transport in the Pancreatic β-Cell: Roles of ZnT (SLC30A) and ZiP (SLC39A) Family Members. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_499

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