Table of Contents Author Guidelines Submit a Manuscript
Journal of Nutrition and Metabolism
Volume 2012, Article ID 173712, 13 pages
http://dx.doi.org/10.1155/2012/173712
Review Article

Zinc Transporters, Mechanisms of Action and Therapeutic Utility: Implications for Type 2 Diabetes Mellitus

1School of Health Sciences, University of Ballarat, University Drive, Mount Helen, VIC 3350, Australia
2Collaborative Research Network, University of Ballarat, Mount Helen, VIC 3350, Australia

Received 4 September 2012; Revised 7 November 2012; Accepted 7 November 2012

Academic Editor: Samir Samman

Copyright © 2012 Stephen A. Myers et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. Charbonnel and B. Cariou, “Pharmacological management of type 2 diabetes: the potential of incretin-based therapies,” Diabetes, Obesity and Metabolism, vol. 13, no. 2, pp. 99–117, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. E. E. Wright, A. H. Stonehouse, and R. M. Cuddihy, “In support of an early polypharmacy approach to the treatment of type 2 diabetes,” Diabetes, Obesity and Metabolism, vol. 12, no. 11, pp. 929–940, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. J. Jansen, W. Karges, and L. Rink, “Zinc and diabetes—clinical links and molecular mechanisms,” The Journal of Nutritional Biochemistry, vol. 20, no. 6, pp. 399–417, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. J. E. Shaw, R. A. Sicree, and P. Z. Zimmet, “Global estimates of the prevalence of diabetes for 2010 and 2030,” Diabetes Research and Clinical Practice, vol. 87, no. 1, pp. 4–14, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Youngman, “Diabetes and renal failure,” in Advanced Renal Care, pp. 122–133, Blackwell Publishing, 2008. View at Google Scholar
  6. Y. Lin and Z. Sun, “Current views on type 2 diabetes,” Journal of Endocrinology, vol. 204, no. 1, pp. 1–11, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. D. C. Patel, C. Albrecht, D. Pavitt et al., “Type 2 diabetes is associated with reduced ATP-binding cassette transporter A1 gene expression, protein and function,” PLoS One, vol. 6, no. 7, Article ID e22142, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. U. J. Kommoju and B. M. Reddy, “Genetic etiology of type 2 diabetes mellitus: a review,” International Journal of Diabetes in Developing Countries, vol. 31, pp. 51–64, 2011. View at Google Scholar
  9. J. Jansen, E. Rosenkranz, S. Overbeck et al., “Disturbed Zinc homeostasis in diabetic patients by in vitro and in vivo analysis of insulinomimetic activity of Zinc,” The Journal of Nutritional Biochemistry, vol. 23, pp. 1458–1466, 2012. View at Google Scholar
  10. D. Scott, “Crystalline insulin,” The Biochemical Journal, vol. 28, pp. 1592–1602, 1934. View at Google Scholar
  11. P. J. Little, R. Bhattacharya, A. E. Moreyra, and I. L. Korichneva, “Zinc and cardiovascular disease,” Nutrition, vol. 26, no. 11-12, pp. 1050–1057, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. S. L. Kelleher, N. H. McCormick, V. Velasquez, and V. Lopez, “Zinc in specialized secretory tissues: roles in the pancreas, prostate, and mammary gland,” Advances in Nutrition, vol. 2, pp. 101–111, 2011. View at Google Scholar
  13. N. Stadler, S. Heeneman, S. Voo et al., “Reduced metal ion concentrations in atherosclerotic plaques from subjects with type 2 diabetes mellitus,” Atherosclerosis, vol. 222, pp. 512–518, 2012. View at Google Scholar
  14. S. Ferdousi and A. R. Mia, “Serum levels of copper and Zinc in newly diagnosed type-2 diabetic subjects,” Mymensingh Medical Journal, vol. 21, pp. 475–478, 2012. View at Google Scholar
  15. M. Basaki, M. Saeb, S. Nazifi, and H. A. Shamsaei, “Zinc, Copper, Iron, and Chromium concentrations in young patients with type 2 diabetes mellitus,” Biological Trace Element Research, vol. 148, pp. 161–164, 2012. View at Google Scholar
  16. Y. Yoshikawa, H. Sakurai, and H. Yasui, “Challenge of studies on the development of new Zn complexes to treat diabetes mellitus,” Journal of the Pharmaceutical Society of Japan, vol. 131, no. 6, pp. 925–930, 2011. View at Publisher · View at Google Scholar · View at Scopus
  17. S. Ruchi and K. Ashok, “A study of age related decrease in Zinc and Chromium and its correlations with type 2 diabetes mellitus,” Research Journal of Chemistry and Environment, vol. 15, pp. 75–80, 2011. View at Google Scholar
  18. J. Rungby, “Zinc, Zinc transporters and diabetes,” Diabetologia, vol. 53, no. 8, pp. 1549–1551, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. A. K. Jayaraman and S. Jayaraman, “Increased level of exogenous Zinc induces cytotoxicity and up-regulates the expression of the ZnT-1 Zinc transporter gene in pancreatic cancer cells,” The Journal of Nutritional Biochemistry, vol. 22, no. 1, pp. 79–88, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. C. Hogstrand, P. Kille, R. I. Nicholson, and K. M. Taylor, “Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine kinase activation,” Trends in Molecular Medicine, vol. 15, no. 3, pp. 101–111, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. A. J. Delli, F. Vaziri-Sani, B. Lindblad et al., “Zinc transporter 8 autoantibodies and their association with SLC30A8 and HLA-DQ genes differ between immigrant and Swedish patients with newly diagnosed type 1 diabetes in the better diabetes diagnosis study,” Diabetes, vol. 10, pp. 2556–2564, 2012. View at Google Scholar
  22. E. Kawasaki, K. Nakamura, G. Kuriya et al., “Differences in the humoral autoreactivity to Zinc transporter 8 between childhood- and adult-onset type 1 diabetes in Japanese patients,” Clinical Immunology, vol. 138, no. 2, pp. 146–153, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. N. Patrushev, B. Seidel-Rogol, and G. Salazar, “Angiotensin II requires Zinc and downregulation of the Zinc transporters ZnT3 and ZnT10 to induce senescence of vascular smooth muscle cells,” PLoS One, vol. 7, Article ID e33211, 2012. View at Google Scholar
  24. M. Foster and S. Samman, “Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus,” Antioxidants & Redox Signaling, vol. 13, no. 10, pp. 1549–1573, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. G. Lyubartseva, J. L. Smith, W. R. Markesbery, and M. A. Lovell, “Alterations of Zinc transporter proteins ZnT-1, ZnT-4 and ZnT-6 in preclinical Alzheimer's disease brain,” Brain Pathology, vol. 20, no. 2, pp. 343–350, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. C. Devirgiliis, P. D. Zalewski, G. Perozzi, and C. Murgia, “Zinc fluxes and Zinc transporter genes in chronic diseases,” Mutation Research, vol. 622, no. 1-2, pp. 84–93, 2007. View at Publisher · View at Google Scholar · View at Scopus
  27. C. Chasapis, A. Loutsidou, C. Spiliopoulou, and M. Stefanidou, “Zinc and human health: an update,” Archives of Toxicology, vol. 86, pp. 1–14, 2011. View at Google Scholar
  28. W. Maret, “Metals on the move: Zinc ions in cellular regulation and in the coordination dynamics of Zinc proteins,” BioMetals, vol. 24, no. 3, pp. 411–418, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. W. Maret, “New perspectives of Zinc coordination environments in proteins,” Journal of Inorganic Biochemistry, vol. 111, pp. 110–116, 2011. View at Google Scholar
  30. T. Fukada, S. Yamasaki, K. Nishida, M. Murakami, and T. Hirano, “Zinc homeostasis and signaling in health and diseases—Zinc signaling,” Journal of Biological Inorganic Chemistry, vol. 16, pp. 1123–1134, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Lu and D. Fu, “Structure of the Zinc transporter YiiP,” Science, vol. 317, no. 5845, pp. 1746–1748, 2007. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Andreini, L. Banci, I. Bertini, and A. Rosato, “Counting the Zinc-proteins encoded in the human genome,” Journal of Proteome Research, vol. 5, no. 1, pp. 196–201, 2006. View at Publisher · View at Google Scholar · View at Scopus
  33. E. Mocchegiani, R. Giacconi, and M. Malavolta, “Zinc signalling and subcellular distribution: emerging targets in type 2 diabetes,” Trends in Molecular Medicine, vol. 14, no. 10, pp. 419–428, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. T. Kambe, “An overview of a wide range of functions of ZnT and Zip Zinc transporters in the secretory pathway,” Bioscience, Biotechnology and Biochemistry, vol. 75, no. 6, pp. 1036–1043, 2011. View at Publisher · View at Google Scholar · View at Scopus
  35. D. Beyersmann and H. Haase, “Functions of Zinc in signaling, proliferation and differentiation of mammalian cells,” BioMetals, vol. 14, no. 3-4, pp. 331–341, 2001. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Vašák and D. W. Hasler, “Metallothioneins: new functional and structural insights,” Current Opinion in Chemical Biology, vol. 4, no. 2, pp. 177–183, 2000. View at Publisher · View at Google Scholar · View at Scopus
  37. H. Haase and L. Rink, Zinc Signaling. Zinc in Human Health, IOS Press, Amsterdam, Netherlands, 2011.
  38. L. A. Lichten and R. J. Cousins, “Mammalian Zinc transporters: nutritional and physiologic regulation,” Annual Review of Nutrition, vol. 29, pp. 153–176, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. J. P. Liuzzi and R. J. Cousins, “Mammalian Zinc transporters,” Annual Review of Nutrition, vol. 24, pp. 151–172, 2004. View at Publisher · View at Google Scholar · View at Scopus
  40. D. J. Eide, “Zinc transporters and the cellular trafficking of Zinc,” Biochimica et Biophysica Acta, vol. 1763, no. 7, pp. 711–722, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. A. B. Petersen, K. Smidt, N. E. Magnusson, F. Moore, L. Egefjord, and J. Rungby, “siRNA-mediated knock-down of ZnT3 and ZnT8 affects production and secretion of insulin and apoptosis in INS-1E cells,” Acta Pathologica, Microbiologica et Immunologica Scandinavica, vol. 119, no. 2, pp. 93–102, 2011. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Nishimura and S. Naito, “Tissue-specific mRNA expression profiles of human solute carrier transporter superfamilies,” Drug Metabolism and Pharmacokinetics, vol. 23, no. 1, pp. 22–44, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. M. Foster, D. Hancock, P. Petocz, and S. Samman, “Zinc transporter genes are coordinately expressed in men and women independently of dietary or plasma Zinc,” The Journal of Nutrition, vol. 141, no. 6, pp. 1195–1201, 2011. View at Publisher · View at Google Scholar · View at Scopus
  44. H. Zhao and D. Eide, “The yeast ZRT1 gene encodes the Zinc transporter protein of a high-affinity uptake system induced by Zinc limitation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 6, pp. 2454–2458, 1996. View at Google Scholar · View at Scopus
  45. D. Eide, M. Broderius, J. Fett, and M. L. Guerinot, “A novel iron-regulated metal transporter from plants identified by functional expression in yeast,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 11, pp. 5624–5628, 1996. View at Publisher · View at Google Scholar · View at Scopus
  46. D. J. Eide, “The SLC39 family of metal ion transporters,” Pflügers Archiv, vol. 447, no. 5, pp. 796–800, 2004. View at Publisher · View at Google Scholar · View at Scopus
  47. R. S. Gitan, M. Shababi, M. Kramer, and D. J. Eide, “A cytosolic domain of the yeast Zrt1 Zinc transporter is required for its post-translational inactivation in response to Zinc and cadmium,” The Journal of Biological Chemistry, vol. 278, no. 41, pp. 39558–39564, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. X. Mao, B.-E. Kim, F. Wang, D. J. Eide, and M. J. Petris, “A histidine-rich cluster mediates the ubiquitination and degradation of the human Zinc transporter, hZIP4, and protects against Zinc cytotoxicity,” The Journal of Biological Chemistry, vol. 282, no. 10, pp. 6992–7000, 2007. View at Publisher · View at Google Scholar · View at Scopus
  49. R. D. Palmiter and S. D. Findley, “Cloning and functional characterization of a mammalian Zinc transporter that confers resistance to Zinc,” EMBO Journal, vol. 14, no. 4, pp. 639–649, 1995. View at Google Scholar · View at Scopus
  50. I. Sekler, S. L. Sensi, M. Hershfinkel, and W. F. Silverman, “Mechanism and regulation of cellular Zinc transport,” Molecular Medicine, vol. 13, no. 7-8, pp. 337–343, 2007. View at Publisher · View at Google Scholar · View at Scopus
  51. H. Haase and W. Maret, “Intracellular Zinc fluctuations modulate protein tyrosine phosphatase activity in insulin/insulin-like growth factor-1 signaling,” Experimental Cell Research, vol. 291, no. 2, pp. 289–298, 2003. View at Publisher · View at Google Scholar · View at Scopus
  52. R. D. Palmiter and L. Huang, “Efflux and compartmentalization of Zinc by members of the SLC30 family of solute carriers,” Pflügers Archiv, vol. 447, no. 5, pp. 744–751, 2004. View at Publisher · View at Google Scholar · View at Scopus
  53. T. Kambe, H. Narita, Y. Yamaguchi-Iwai et al., “Cloning and characterization of a novel mammalian Zinc transporter, Zinc transporter 5, abundantly expressed in pancreatic β cells,” The Journal of Biological Chemistry, vol. 277, no. 21, pp. 19049–19055, 2002. View at Publisher · View at Google Scholar · View at Scopus
  54. L. Huang, C. P. Kirschke, and J. Gitschier, “Functional characterization of a novel mammalian Zinc transporter, ZnT6,” The Journal of Biological Chemistry, vol. 277, no. 29, pp. 26389–26395, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. A. Fukunaka, T. Suzuki, Y. Kurokawa et al., “Demonstration and characterization of the heterodimerization of ZnT5 and ZnT6 in the early secretory pathway,” The Journal of Biological Chemistry, vol. 284, no. 45, pp. 30798–30806, 2009. View at Publisher · View at Google Scholar · View at Scopus
  56. R. J. Cousins, J. P. Liuzzi, and L. A. Lichten, “Mammalian Zinc transport, trafficking, and signals,” The Journal of Biological Chemistry, vol. 281, no. 34, pp. 24085–24089, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. F. Chimienti, S. Devergnas, F. Pattou et al., “In vivo expression and functional characterization of the Zinc transporter ZnT8 in glucose-induced insulin secretion,” Journal of Cell Science, vol. 119, no. 20, pp. 4199–4206, 2006. View at Publisher · View at Google Scholar · View at Scopus
  58. D. Mohanasundaram, C. Drogemuller, J. Brealey et al., “Ultrastructural analysis, Zinc transporters, glucose transporters and hormones expression in new world primate (Callithrix jacchus) and human pancreatic islets,” General and Comparative Endocrinology, vol. 174, pp. 71–79, 2011. View at Google Scholar
  59. L. Huang and C. P. Kirschke, “A di-leucine sorting signal in ZIP1 (SLC39A1) mediates endocytosis of the protein,” The FEBS Journal, vol. 274, no. 15, pp. 3986–3997, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. F. Wang, J. Dufner-Beattie, B.-E. Kim, M. J. Petris, G. Andrews, and D. J. Eide, “Zinc-stimulated endocytosis controls activity of the mouse ZIP1 and ZIP3 Zinc uptake transporters,” The Journal of Biological Chemistry, vol. 279, no. 23, pp. 24631–24639, 2004. View at Publisher · View at Google Scholar · View at Scopus
  61. R. B. Franklin, P. Feng, B. Milon et al., “hZIP1 Zinc uptake transporter down regulation and Zinc depletion in prostate cancer,” Molecular Cancer, vol. 4, article 32, 2005. View at Publisher · View at Google Scholar · View at Scopus
  62. K. W. Leung, A. Gvritishvili, Y. Liu, and J. Tombran-Tink, “ZIP2 and ZIP4 mediate age-related Zinc fluxes across the retinal pigment epithelium,” Journal of Molecular Neuroscience, vol. 46, pp. 122–137, 2012. View at Publisher · View at Google Scholar · View at Scopus
  63. R. Giacconi, E. Muti, M. Malavolta et al., “A novel Zip2 Gln/Arg/Leu codon 2 polymorphism is associated with carotid artery disease in aging,” Rejuvenation Research, vol. 11, no. 2, pp. 297–300, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. J. L. Peters, J. Dufner-Beattie, W. Xu et al., “Targeting of the mouse Slc39a2 (Zip2) gene reveals highly cell-specific patterns of expression, and unique functions in Zinc, iron, and calcium homeostasis,” Genesis, vol. 45, no. 6, pp. 339–352, 2007. View at Publisher · View at Google Scholar · View at Scopus
  65. S. L. Kelleher and B. Lönnerdal, “Zip3 plays a major role in Zinc uptake into mammary epithelial cells and is regulated by prolactin,” American Journal of Physiology, vol. 288, no. 5, pp. C1042–C1047, 2005. View at Publisher · View at Google Scholar · View at Scopus
  66. V. Yuzbasiyan-Gurkan and E. Bartlett, “Identification of a unique splice site variant in SLC39A4 in bovine hereditary Zinc deficiency, lethal trait A46: an animal model of acrodermatitis enteropathica,” Genomics, vol. 88, no. 4, pp. 521–526, 2006. View at Publisher · View at Google Scholar · View at Scopus
  67. T. Donahue and O. J. Hines, “The ZIP4 pathway in pancreatic cancer,” Cancer Biology & Therapy, vol. 9, no. 3, pp. 243–245, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. F. Wang, B. E. Kim, M. J. Petris, and D. J. Eide, “The mammalian Zip5 protein is a Zinc transporter that localizes to the basolateral surface of polarized cells,” The Journal of Biological Chemistry, vol. 279, no. 49, pp. 51433–51441, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. B. P. Weaver and G. K. Andrews, “Regulation of Zinc-responsive Slc39a5 (Zip5) translation is mediated by conserved elements in the 3'-untranslated region,” BioMetals, vol. 25, pp. 319–335, 2012. View at Google Scholar
  70. K. M. Taylor, “A distinct role in breast cancer for two LIV-1 family Zinc transporters,” Biochemical Society Transactions, vol. 36, no. 6, pp. 1247–1251, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. L. Huang, C. P. Kirschke, Y. Zhang, and Y. Y. Yan, “The ZIP7 gene (Slc39a7) encodes a Zinc transporter involved in Zinc homeostasis of the Golgi apparatus,” The Journal of Biological Chemistry, vol. 280, no. 15, pp. 15456–15463, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. K. M. Taylor, P. Vichova, N. Jordan, S. Hiscox, R. Hendley, and R. I. Nicholson, “ZIP7-mediated intracellular Zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer cells,” Endocrinology, vol. 149, no. 10, pp. 4912–4920, 2008. View at Publisher · View at Google Scholar · View at Scopus
  73. C.-Y. Wang, S. Jenkitkasemwong, S. Duarte et al., “ZIP8 is an Iron and Zinc transporter whose cell-surface expression is upregulated by cellular iron loading,” The Journal of Biological Chemistry, vol. 287, pp. 34032–34043, 2012. View at Google Scholar
  74. L. He, K. Girijashanker, T. P. Dalton et al., “ZIP8, member of the solute-carrier-39 (SLC39) metal-transporter family:characterization of transporter properties,” Molecular Pharmacology, vol. 70, no. 1, pp. 171–180, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. W. Matsuura, T. Yamazaki, Y. I. Yuko et al., “SLC39A9 (ZIP9) regulates Zinc homeostasis in the secretory pathway: characterization of the zip subfamily i protein in vertebrate cells,” Bioscience, Biotechnology and Biochemistry, vol. 73, no. 5, pp. 1142–1148, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. N. Kagara, N. Tanaka, S. Noguchi, and T. Hirano, “Zinc and its transporter ZIP10 are involved in invasive behavior of breast cancer cells,” Cancer Science, vol. 98, no. 5, pp. 692–697, 2007. View at Publisher · View at Google Scholar · View at Scopus
  77. P. Kaler and R. Prasad, “Molecular cloning and functional characterization of novel Zinc transporter rZip10 (Slc39a10) involved in Zinc uptake across rat renal brush-border membrane,” American Journal of Physiology, vol. 292, no. 1, pp. F217–F229, 2007. View at Publisher · View at Google Scholar · View at Scopus
  78. S. L. Kelleher, V. Velasquez, T. P. Croxford, N. H. McCormick, V. Lopez, and J. MacDavid, “Mapping the Zinc-transporting system in mammary cells: molecular analysis reveals a phenotype-dependent Zinc-transporting network during lactation,” Journal of Cellular Physiology, vol. 227, pp. 1761–1770, 2012. View at Google Scholar
  79. M. Bly, “Examination of the Zinc transporter gene, SLC39A12,” Schizophrenia Research, vol. 81, no. 2-3, pp. 321–322, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. T. Fukada, N. Civic, T. Furuichi et al., “The Zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-β signaling pathways,” PLoS One, vol. 3, no. 11, Article ID e3642, 2008. View at Publisher · View at Google Scholar · View at Scopus
  81. B. H. Bin, T. Fukada, T. Hosaka et al., “Biochemical characterization of human ZIP13 protein: a homo-dimerized Zinc transporter involved in the spondylocheiro dysplastic Ehlers-Danlos syndrome,” The Journal of Biological Chemistry, vol. 286, pp. 40255–40265, 2011. View at Google Scholar
  82. C. Lang, C. Murgia, M. Leong et al., “Anti-inflammatory effects of Zinc and alterations in Zinc transporter mRNA in mouse models of allergic inflammation,” American Journal of Physiology, vol. 292, no. 2, pp. L577–L584, 2007. View at Publisher · View at Google Scholar · View at Scopus
  83. K. Girijashanker, L. He, M. Soleimani et al., “Slc39a14 gene encodes ZIP14, a metal/bicarbonate symporter: similarities to the ZIP8 transporter,” Molecular Pharmacology, vol. 73, pp. 1413–1423, 2008. View at Google Scholar · View at Scopus
  84. R. D. Palmiter, T. B. Cole, and S. D. Findley, “ZnT-2, a mammalian protein that confers resistance to Zinc by facilitating vesicular sequestration,” EMBO Journal, vol. 15, no. 8, pp. 1784–1791, 1996. View at Google Scholar · View at Scopus
  85. R. D. Palmiter, T. B. Cole, C. J. Quaife, and S. D. Findley, “ZnT-3, a putative transporter of Zinc into synaptic vesicles,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 25, pp. 14934–14939, 1996. View at Publisher · View at Google Scholar · View at Scopus
  86. N. Beyer, D. T. R. Coulson, S. Heggarty et al., “ZnT3 mRNA levels are reduced in Alzheimer's disease post-mortem brain,” Molecular Neurodegeneration, vol. 4, article 53, 2009. View at Publisher · View at Google Scholar · View at Scopus
  87. L. Huang and J. Gitschier, “A novel gene involved in Zinc transport is deficient in the lethal milk mouse,” Nature Genetics, vol. 17, no. 3, pp. 292–297, 1997. View at Publisher · View at Google Scholar · View at Scopus
  88. K. Inoue, K. Matsuda, M. Itoh et al., “Osteopenia and male-specific sudden cardiac death in mice lacking a Zinc transporter gene, Znt5,” Human Molecular Genetics, vol. 11, no. 15, pp. 1775–1784, 2002. View at Google Scholar · View at Scopus
  89. C. P. Kirschke and L. Huang, “ZnT7, a novel mammalian Zinc transporter, accumulates Zinc in the Golgi apparatus,” The Journal of Biological Chemistry, vol. 278, no. 6, pp. 4096–4102, 2003. View at Publisher · View at Google Scholar · View at Scopus
  90. S. Tepaamorndech, L. Huang, and C. P. Kirschke, “A null-mutation in the Znt7 gene accelerates prostate tumor formation in a transgenic adenocarcinoma mouse prostate model,” Cancer Letters, vol. 308, pp. 33–42, 2011. View at Google Scholar
  91. J. Xu, J. Wang, and B. Chen, “SLC30A8 (ZnT8) variations and type 2 diabetes in the Chinese Han population,” Genetics and Molecular Research, vol. 11, pp. 1592–1598, 2012. View at Google Scholar
  92. J. M. Howson, S. Krause, H. Stevens et al., “Genetic association of Zinc transporter 8 (ZnT8) autoantibodies in type 1 diabetes cases,” Diabetologia, vol. 55, pp. 1978–1984, 2012. View at Google Scholar
  93. D. L. C. Sim and V. T. K. Chow, “The novel human HUEL (C4orf1) gene maps to chromosome 4p12-p13 and encodes a nuclear protein containing the nuclear receptor interaction motif,” Genomics, vol. 59, no. 2, pp. 224–233, 1999. View at Publisher · View at Google Scholar · View at Scopus
  94. M. Stamelou, K. Tuschl, W. K. Chong et al., “Dystonia with brain manganese accumulation resulting from SLC30A10 mutations: a new treatable disorder,” Movement Disorders, vol. 27, pp. 1317–1322, 2012. View at Google Scholar
  95. K. Tuschl, P. T. Clayton, S. M. Gospe Jr. et al., “Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man,” American Journal of Human Genetics, vol. 90, pp. 457–466, 2012. View at Google Scholar
  96. M. Quadri, A. Federico, T. Zhao et al., “Mutations in SLC30A10 cause parkinsonism and dystonia with hypermanganesemia, polycythemia, and chronic liver disease,” American Journal of Human Genetics, vol. 90, pp. 467–477, 2012. View at Google Scholar
  97. R. D. Andersen, B. W. Birren, T. Ganz, J. E. Piletz, and H. R. Herschman, “Molecular cloning of the rat metallothionein 1 (MT-1) mRNA sequence,” DNA, vol. 2, no. 1, pp. 15–22, 1983. View at Google Scholar · View at Scopus
  98. M. Levadoux-Martin, J. E. Hesketh, J. H. Beattie, and H. M. Wallace, “Influence of metallothionein-1 localization on its function,” The Biochemical Journal, vol. 355, no. 2, pp. 473–479, 2001. View at Publisher · View at Google Scholar · View at Scopus
  99. H. Kurita, S. Ohsako, S. I. Hashimoto, J. Yoshinaga, and C. Tohyama, “Prenatal Zinc deficiency-dependent epigenetic alterations of mouse metallothioneins-2 gene,” The Journal of Nutrional Biochemistry, vol. 24, no. 1, pp. 256–266, 2013. View at Google Scholar
  100. A. Santon, G. C. Sturniolo, V. Albergoni, and P. Irato, “Metallothionein-1 and metallothionein-2 gene expression and localisation of apoptotic cells in Zn-treated LEC rat liver,” Histochemistry and Cell Biology, vol. 119, no. 4, pp. 301–308, 2003. View at Google Scholar · View at Scopus
  101. Y. Manso, J. Carrasco, G. Comes et al., “Characterization of the role of metallothionein-3 in an animal model of Alzheimer's disease,” Cellular and Molecular Life Sciences, vol. 69, pp. 3683–3700, 2012. View at Google Scholar
  102. H. I. Chen, Y. W. Chiu, Y. K. Hsu, W. F. Li, Y. C. Chen, and H. Y. Chuang, “The association of metallothionein-4 gene polymorphism and renal function in long-term lead-exposed workers,” Biological Trace Element Research, vol. 137, no. 1, pp. 55–62, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. G. Meloni, K. Zovo, J. Kazantseva, P. Palumaa, and M. Vašák, “Organization and assembly of metal-thiolate clusters in epithelium-specific metallothionein-4,” The Journal of Biological Chemistry, vol. 281, no. 21, pp. 14588–14595, 2006. View at Publisher · View at Google Scholar · View at Scopus
  104. L. A. Gaither and D. J. Eide, “Eukaryotic Zinc transporters and their regulation,” BioMetals, vol. 14, no. 3-4, pp. 251–270, 2001. View at Publisher · View at Google Scholar · View at Scopus
  105. S. Yamasaki, K. Sakata-Sogawa, A. Hasegawa et al., “Zinc is a novel intracellular second messenger,” The Journal of Cell Biology, vol. 177, no. 4, pp. 637–645, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. T. Hirano, M. Murakami, T. Fukada, K. Nishida, S. Yamasaki, and T. Suzuki, “Roles of Zinc and Zinc signaling in immunity: Zinc as an intracellular signaling molecule,” in Advances in Immunology, W. A. Frederick, Ed., vol. 97, pp. 149–176, Academic Press, 2008. View at Google Scholar
  107. L. Coulston and P. Dandona, “Insulin-like effect of Zinc on adipocytes,” Diabetes, vol. 29, no. 8, pp. 665–667, 1980. View at Google Scholar · View at Scopus
  108. J. M. May and C. S. Contoreggi, “The mechanism of the insulin-like effects of ionic Zinc,” The Journal of Biological Chemistry, vol. 257, no. 8, pp. 4362–4368, 1982. View at Google Scholar · View at Scopus
  109. O. Ezaki, “IIb group metal ions (Zn2+, Cd2+, Hg2+) stimulate glucose transport activity by post-insulin receptor kinase mechanism in rat adipocytes,” The Journal of Biological Chemistry, vol. 264, no. 27, pp. 16118–16122, 1989. View at Google Scholar · View at Scopus
  110. X. H. Tang and N. F. Shay, “Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes,” The Journal of Nutrition, vol. 131, no. 5, pp. 1414–1420, 2001. View at Google Scholar · View at Scopus
  111. H. Haase and W. Maret, “Fluctuations of cellular, available Zinc modulate insulin signaling via inhibition of protein tyrosine phosphatases,” Journal of Trace Elements in Medicine and Biology, vol. 19, no. 1, pp. 37–42, 2005. View at Publisher · View at Google Scholar · View at Scopus
  112. Y.-M. Ma, R.-Y. Tao, Q. Liu et al., “PTP1B inhibitor improves both insulin resistance and lipid abnormalities in vivo and in vitro,” Molecular and Cellular Biochemistry, vol. 357, pp. 65–72, 2011. View at Publisher · View at Google Scholar · View at Scopus
  113. B. Xue, Y.-B. Kim, A. Lee et al., “Protein-tyrosine phosphatase 1B deficiency reduces insulin resistance and the diabetic phenotype in mice with polygenic insulin resistance,” The Journal of Biological Chemistry, vol. 282, no. 33, pp. 23829–23840, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. A. González-Rodríguez, J. A. M. Gutierrez, S. Sanz-González, M. Ros, D. J. Burks, and Á. M. Valverde, “Inhibition of PTP1B restores IRS1-mediated hepatic insulin signaling in IRS2-deficient mice,” Diabetes, vol. 59, no. 3, pp. 588–599, 2010. View at Publisher · View at Google Scholar · View at Scopus
  115. R. Ilouz, O. Kaidanovich, D. Gurwitz, and H. Eldar-Finkelman, “Inhibition of glycogen synthase kinase-3β by bivalent Zinc ions: insight into the insulin-mimetic action of Zinc,” Biochemical and Biophysical Research Communications, vol. 295, no. 1, pp. 102–106, 2002. View at Publisher · View at Google Scholar · View at Scopus
  116. T. Moniz, M. J. Amorim, R. Ferreira et al., “Investigation of the insulin-like properties of Zinc(II) complexes of 3-hydroxy-4-pyridinones: identification of a compound with glucose lowering effect in STZ-induced type I diabetic animals,” Journal of Inorganic Biochemistry, vol. 105, pp. 1675–1682, 2011. View at Google Scholar
  117. S. F. Simon and C. G. Taylor, “Dietary Zinc supplementation attenuates hyperglycemia in db/db mice,” Proceedings of the Society for Experimental Biology and Medicine, vol. 226, no. 1, pp. 43–51, 2001. View at Google Scholar · View at Scopus
  118. N. Wijesekara, F. Chimienti, and M. B. Wheeler, “Zinc, a regulator of islet function and glucose homeostasis,” Diabetes, Obesity and Metabolism, vol. 11, no. 4, pp. 202–214, 2009. View at Publisher · View at Google Scholar · View at Scopus
  119. Y. Yoshikawa, E. Ueda, Y. Kojima, and H. Sakurai, “The action mechanism of Zinc(II) complexes with insulinomimetic activity in rat adipocytes,” Life Sciences, vol. 75, no. 6, pp. 741–751, 2004. View at Publisher · View at Google Scholar · View at Scopus
  120. Y. Zhao, Y. Tan, J. Dai et al., “Zinc deficiency exacerbates diabetic down-regulation of Akt expression and function in the testis: essential roles of PTEN, PTP1B and TRB3,” The Journal of Nutritional Biochemistry, vol. 23, no. 8, pp. 1018–1026, 2012. View at Google Scholar
  121. N. R. Pandey, G. Vardatsikos, M. Z. Mehdi, and A. K. Srivastava, “Cell-type-specific roles of IGF-1R and EGFR in mediating Zn2+ -induced ERK1/2 and PKB phosphorylation,” Journal of Biological Inorganic Chemistry, vol. 15, no. 3, pp. 399–407, 2010. View at Publisher · View at Google Scholar · View at Scopus
  122. J. C. Rutherford and A. J. Bird, “Metal-responsive transcription factors that regulate Iron, Zinc, and Copper homeostasis in eukaryotic cells,” Eukaryotic Cell, vol. 3, no. 1, pp. 1–13, 2004. View at Publisher · View at Google Scholar · View at Scopus
  123. I. Hwang, T. Yoon, C. Kim, B. Cho, S. Lee, and M. K. Song, “Different roles of Zinc plus arachidonic acid on insulin sensitivity between high fructose- and high fat-fed rats,” Life Sciences, vol. 88, no. 5-6, pp. 278–284, 2011. View at Publisher · View at Google Scholar · View at Scopus
  124. K. F. Petersen, S. Dufour, D. B. Savage et al., “The role of skeletal muscle insulin resistance in the pathogenesis of the metabolic syndrome,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 31, pp. 12587–12594, 2007. View at Publisher · View at Google Scholar · View at Scopus
  125. M. Peppa, C. Koliaki, P. Nikolopoulos, and S. A. Raptis, “Skeletal muscle insulin resistance in endocrine disease,” Journal of Biomedicine and Biotechnology, vol. 2010, Article ID 527850, 13 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
  126. Y. A. Seo, V. Lopez, and S. L. Kelleher, “A histidine-rich motif mediates mitochondrial localization of ZnT2 to modulate mitochondrial function,” American Journal of Physiology, vol. 300, no. 6, pp. C1479–C1489, 2011. View at Publisher · View at Google Scholar · View at Scopus
  127. J. P. Liuzzi, R. K. Blanchard, and R. J. Cousins, “Differential regulation of Zinc transporter 1, 2, and 4 mRNA expression by dietary Zinc in rats,” The Journal of Nutrition, vol. 131, no. 1, pp. 46–52, 2001. View at Google Scholar · View at Scopus
  128. F. Radtke, R. Heuchel, O. Georgiev et al., “Cloned transcription factor MTF-1 activates the mouse metallothionein I promoter,” EMBO Journal, vol. 12, no. 4, pp. 1355–1362, 1993. View at Google Scholar · View at Scopus
  129. S. J. Langmade, R. Ravindra, P. J. Daniels, and G. K. Andrews, “The transcription factor MTF-1 mediates metal regulation of the mouse ZnT1 gene,” The Journal of Biological Chemistry, vol. 275, no. 44, pp. 34803–34809, 2000. View at Google Scholar · View at Scopus
  130. R. A. Cragg, G. R. Christie, S. R. Phillips et al., “A novel Zinc-regulated human Zinc transporter, hZTL1, is localized to the enterocyte apical membrane,” The Journal of Biological Chemistry, vol. 277, no. 25, pp. 22789–22797, 2002. View at Publisher · View at Google Scholar · View at Scopus
  131. L. C. Costellot, Y. Liu, J. Zou, and R. B. Franklin, “Evidence for a Zinc uptake transporter in human prostate cancer cells which is regulated by prolactin and testosterone,” The Journal of Biological Chemistry, vol. 274, no. 25, pp. 17499–17504, 1999. View at Publisher · View at Google Scholar · View at Scopus
  132. K. M. Taylor, H. E. Morgan, K. Smart et al., “The emerging role of the LIV-1 subfamily of Zinc transporters in breast cancer,” Molecular Medicine, vol. 13, no. 7-8, pp. 396–406, 2007. View at Publisher · View at Google Scholar · View at Scopus
  133. B. Besecker, S. Bao, B. Bohacova, A. Papp, W. Sadee, and D. L. Knoell, “The human Zinc transporter SLC39A8 (Zip8) is critical in Zinc-mediated cytoprotection in lung epithelia,” American Journal of Physiology, vol. 294, no. 6, pp. L1127–L1136, 2008. View at Publisher · View at Google Scholar · View at Scopus
  134. J. R. Napolitano, M.-J. Liu, S. Bao et al., “Cadmium-mediated toxicity of lung epithelia is enhanced through NF-êB-mediated transcriptional activation of the human Zinc transporter ZIP8,” American Journal of Physiology, vol. 302, pp. L909–L918, 2012. View at Google Scholar
  135. J. P. Liuzzi, L. A. Lichten, S. Rivera et al., “Interleukin-6 regulates the Zinc transporter Zip14 in liver and contributes to the hypoZincemia of the acute-phase response,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 19, pp. 6843–6848, 2005. View at Publisher · View at Google Scholar · View at Scopus
  136. M. Lazarczyk, C. Pons, J.-A. Mendoza, P. Cassonnet, Y. Jacob, and M. Favre, “Regulation of cellular Zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses,” The Journal of Experimental Medicine, vol. 205, no. 1, pp. 35–42, 2008. View at Publisher · View at Google Scholar · View at Scopus
  137. B.-E. Kim, F. Wang, J. Dufner-Beattie, G. K. Andrews, D. J. Eide, and M. J. Petris, “Zn2+-stimulated endocytosis of the mZIP4 Zinc transporter regulates its location at the plasma membrane,” The Journal of Biological Chemistry, vol. 279, no. 6, pp. 4523–4530, 2004. View at Publisher · View at Google Scholar · View at Scopus
  138. T. Suzuki, K. Ishihara, H. Migaki et al., “Zinc transporters, ZnT5 and ZnT7, are required for the activation of alkaline phosphatases, Zinc-requiring enzymes that are glycosylphosphatidylinositol-anchored to the cytoplasmic membrane,” The Journal of Biological Chemistry, vol. 280, no. 1, pp. 637–643, 2005. View at Publisher · View at Google Scholar · View at Scopus
  139. B. Milon, D. Dhermy, D. Pountney, M. Bourgeois, and C. Beaumont, “Differential subcellular localization of hZip1 in adherent and non-adherent cells,” FEBS Letters, vol. 507, no. 3, pp. 241–246, 2001. View at Publisher · View at Google Scholar · View at Scopus
  140. K. M. Taylor, S. Hiscox, R. I. Nicholson, C. Hogstrand, and P. Kille, “Protein kinase CK2 triggers cytosolic Zinc signaling pathways by phosphorylation of Zinc channel ZIP7,” Science Signaling, vol. 5, article 11, 2012. View at Google Scholar
  141. R. Meng, C. Götz, and M. Montenarh Mathias, “The role of protein kinase CK2 in the regulation of the insulin production of pancreatic islets,” Biochemical and Biophysical Research Communications, vol. 401, no. 2, pp. 203–206, 2010. View at Publisher · View at Google Scholar · View at Scopus
  142. C. Taghibiglou, F. Rashid-Kolvear, S. C. Van Iderstine et al., “Hepatic very low density lipoprotein-ApoB overproduction is associated with attenuated hepatic insulin signaling and overexpression of protein-tyrosine phosphatase 1B in a fructose-fed hamster model of insulin resistance,” The Journal of Biological Chemistry, vol. 277, no. 1, pp. 793–803, 2002. View at Publisher · View at Google Scholar · View at Scopus
  143. A. R. Saltiel and J. E. Pessin, “Insulin signaling pathways in time and space,” Trends in Cell Biology, vol. 12, no. 2, pp. 65–71, 2002. View at Publisher · View at Google Scholar · View at Scopus
  144. S. Hojyo, T. Fukada, S. Shimoda et al., “The Zinc transporter SLC39A14/ZIP14 controls G-protein coupled receptor-mediated signaling required for systemic growth,” PLoS One, vol. 6, no. 3, Article ID e18059, 2011. View at Publisher · View at Google Scholar · View at Scopus
  145. S. Tang, H. Le-Tien, B. J. Goldstein, P. Shin, R. Lai, and I. G. Fantus, “Decreased in situ insulin receptor dephosphorylation in hyperglycemia-induced insulin resistance in rat adipocytes,” Diabetes, vol. 50, no. 1, pp. 83–90, 2001. View at Google Scholar · View at Scopus
  146. M. K. Song, M. J. Rosenthal, S. Hong et al., “Synergistic antidiabetic activities of Zinc, cyclo (his-pro), and arachidonic acid,” Metabolism, vol. 50, no. 1, pp. 53–59, 2001. View at Publisher · View at Google Scholar · View at Scopus
  147. J. H. Y. Park, C. J. Grandjean, M. H. Hart, S. H. Erdman, P. Pour, and J. A. Vanderhoof, “Effect of pure Zinc deficiency on glucose tolerance and insulin and glucagon levels,” American Journal of Physiology, vol. 251, no. 3, p. 14/3, 1986. View at Google Scholar · View at Scopus
  148. R. Jayawardena, P. Ranasinghe, P. Galappatthy, R. Malkanthi, G. Constantine, and P. Katulanda, “Effects of Zinc supplementation on diabetes mellitus: a systematic review and meta-analysis,” Diabetology & Metabolic Syndrome, vol. 4, article 13, 2012. View at Google Scholar
  149. J. M. Wenzlau, K. Juhl, L. Yu et al., “The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 43, pp. 17040–17045, 2007. View at Publisher · View at Google Scholar · View at Scopus
  150. Y. Fu, W. Tian, E. B. Pratt et al., “Down-regulation of ZnT8 expression in INS-1 rat pancreatic beta cells reduces insulin content and glucose-inducible insulin secretion,” PLoS One, vol. 4, no. 5, Article ID e5679, 2009. View at Publisher · View at Google Scholar · View at Scopus
  151. N. Wijesekara, F. F. Dai, A. B. Hardy et al., “Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion,” Diabetologia, vol. 53, no. 8, pp. 1656–1668, 2010. View at Publisher · View at Google Scholar · View at Scopus
  152. T. J. Nicolson, E. A. Bellomo, N. Wijesekara 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, vol. 58, no. 9, pp. 2070–2083, 2009. View at Publisher · View at Google Scholar · View at Scopus
  153. L. D. Pound, S. A. Sarkar, R. K. P. Benninger et al., “Deletion of the mouse Slc30a8 gene encoding Zinc transporter-8 results in impaired insulin secretion,” The Biochemical Journal, vol. 421, no. 3, pp. 371–376, 2009. View at Publisher · View at Google Scholar · View at Scopus
  154. A. B. Hardy, N. Wijesekara, I. Genkin et al., “Effects of high-fat diet feeding on Znt8-null mice: differences between beta-cell and global knockout of Znt8,” American Journal of Physiology, vol. 302, pp. E1084–E1096, 2012. View at Google Scholar
  155. R. Sladek, G. Rocheleau, J. Rung et al., “A genome-wide association study identifies novel risk loci for type 2 diabetes,” Nature, vol. 445, no. 7130, pp. 881–885, 2007. View at Publisher · View at Google Scholar · View at Scopus
  156. J. Xu, J. Wang, and B. Chen, “SLC30A8 (ZnT8) variations and type 2 diabetes in the Chinese Han population,” Genetics and Molecular Research, vol. 11, pp. 1592–1598, 2012. View at Google Scholar
  157. R. Saxena, B. F. Voight, V. Lyssenko et al., “Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels,” Science, vol. 316, pp. 1331–1336, 2007. View at Google Scholar
  158. T. W. Boesgaard, J. Žilinskaite, M. Vänttinen et al., “The common SLC30A8 Arg325Trp variant is associated with reduced first-phase insulin release in 846 non-diabetic offspring of type 2 diabetes patients—The EUGENE2 study,” Diabetologia, vol. 51, no. 5, pp. 816–820, 2008. View at Publisher · View at Google Scholar · View at Scopus
  159. L. Huang, M. Yan, and C. P. Kirschke, “Over-expression of ZnT7 increases insulin synthesis and secretion in pancreatic β-cells by promoting insulin gene transcription,” Experimental Cell Research, vol. 316, no. 16, pp. 2630–2643, 2010. View at Publisher · View at Google Scholar · View at Scopus
  160. L. Huang, C. P. Kirschke, Y.-A. E. Lay, L. B. Levy, D. E. Lamirande, and P. H. Zhang, “Znt7-null mice are more susceptible to diet-induced glucose intolerance and insulin resistance,” The Journal of Biological Chemistry, vol. 287, pp. 33883–33896, 2012. View at Google Scholar
  161. K. Smidt, N. Jessen, A. B. Petersen et al., “SLC30A3 responds to glucose- and Zinc variations in β-cells and is critical for insulin production and in vivo glucose-metabolism during β-cell stress,” PLoS One, vol. 4, no. 5, Article ID e5684, 2009. View at Publisher · View at Google Scholar · View at Scopus
  162. E. A. Bellomo, G. Meur, and G. A. Rutter, “Glucose regulates free cytosolic Zn2+ concentration, Slc39 (ZiP), and metallothionein gene expression in primary pancreatic islet β-cells,” The Journal of Biological Chemistry, vol. 286, no. 29, pp. 25778–25789, 2011. View at Publisher · View at Google Scholar · View at Scopus