Zinc and zinc transporter regulation in pancreatic islets and the potential role of zinc in islet transplantation

Review of Diabetic Studies

Volumn 7, Issue 4, 2010, Pages 263-274

  Bosco, Mariea D ^a   Mohanasundaram, Daisy M ^a   Drogemuller, Chris J ^a   Lang, Carol J ^b,c   Zalewski, Peter D ^b,c   Coates, P Toby ^a,b,d  

^a ROYAL ADELAIDE HOSPITAL   (Australia)

^b UNIVERSITY OF ADELAIDE   (Australia)

^c QUEEN ELIZABETH HOSPITAL   (Australia)

^d UNIVERSITY OF ADELAIDE   (Australia)

Author keywords

Apoptosis; Beta cell; Insulin secretion; Oxidative stress; Pancreatic islet; Transplantation; Type 1 diabetes; Zinc transporter; ZIP; ZnT

Indexed keywords

CYTOKINE; UNCLASSIFIED DRUG; ZINC; ZINC EFFLUX TRANSPORTER ZIP1; ZINC EFFLUX TRANSPORTER ZIP10; ZINC EFFLUX TRANSPORTER ZIP14; ZINC EFFLUX TRANSPORTER ZIP3; ZINC EFFLUX TRANSPORTER ZIP4; ZINC EFFLUX TRANSPORTER ZIP5; ZINC EFFLUX TRANSPORTER ZIP7; ZINC INFLUX TRANSPORTER ZNT1; ZINC INFLUX TRANSPORTER ZNT10; ZINC INFLUX TRANSPORTER ZNT2; ZINC INFLUX TRANSPORTER ZNT3; ZINC INFLUX TRANSPORTER ZNT4; ZINC INFLUX TRANSPORTER ZNT5; ZINC INFLUX TRANSPORTER ZNT7; ZINC INFLUX TRANSPORTER ZNT8; ZINC INFLUX TRANSPORTER ZNT9; ZINC TRANSPORTER; CARRIER PROTEIN; INSULIN; ZINC BINDING PROTEIN; ZINC-BINDING PROTEIN;

APOPTOSIS; CELL FUNCTION; CELL SURVIVAL; HUMAN; INFLAMMATION; NONHUMAN; ORGAN DONOR; OXIDATIVE STRESS; PANCREAS ISLET; PANCREAS ISLET TRANSPLANTATION; PROTEIN EXPRESSION; REVIEW; CYTOLOGY; GENETICS; INSULIN DEPENDENT DIABETES MELLITUS; METABOLISM; METHODOLOGY; PANCREAS; PATHOLOGY;

CARRIER PROTEINS; DIABETES MELLITUS, TYPE 1; HUMANS; INSULIN; ISLETS OF LANGERHANS; ISLETS OF LANGERHANS TRANSPLANTATION; PANCREAS; ZINC;

EID: 80055092666     PISSN: 16136071     EISSN: 16140575     Source Type: Journal    
DOI: 10.1900/RDS.2010.7.263     Document Type: Review

References (110)

1. Leitao CB, Cure P, Tharavanij T, Baidal DA, Alejan-dro R. Current challenges in islet transplantation. Curr Diab Rep 2008. 8:324-331.
2. Markmann JF, Deng S, Huang X, Desai NM, Velid-edeoglu EH, Lui C, Frank A, Markmann E, Palanjian M, Brayman K, et al. Insulin independence following isolated islet transplantation and single islet infusions. Ann Surg 2003. 237:741-749.
3. Hering BJ, Kandaswamy R, Ansite JD, Eckman PM, Nakano M, Sawada T, Matsumoto I, Ihm SH, Zhang HJ, Parkey J, Hunter DW, Sutherland DE. Single-donor, marginal-dose islet transplantation in patients with type 1 diabetes. JAMA 2005. 293:830-835.
4. Nagata M, Mullen Y, Matsuo S, Herrera M, Clare-Salzler M. Destruction of islet isografts by severe nonspecific inflammation. Transplant Proc 1990. 22:855-856.
5. Biarnes M, Montolio M, Nacher V, Raurell M, Sole J, Montanya E. Diabetes 2002. 51:66-72.
6. Emamaullee J, Liston P, Korneluk RG, Shapiro AM, Elliott JF. XIAP overexpression in islet beta-cells enhances engraftment and minimizes hypoxia-reperfusion injury. Am J Transplant 2005. 5:1297-1305.
7. Ynsa MD, Ren MQ, Rajendran R, Sidhapuriwala JN, van Kan JA, Bhatia M, Watt F. Zinc mapping and density imaging of rabbit pancreas endocrine tissue sections using nuclear microscopy. Microsc Microanal 2009. 15:345-352.
8. Guo L, Lichten LA, Ryu MS, Liuzzi JP, Wang F, Cousins RJ. STAT5-glucocorticoid receptor interaction and MTF-1 regulate the expression of ZnT2 (Slc30a2) in pancreatic acinar cells. Proc Natl Acad Sci U S A 2010. 107:2818-2823.
9. Hambidge KM, Miller LV, Westcott JE, Sheng X, Krebs NF. Zinc bioavailability and homeostasis. Am J Clin Nutr 2010. 91:1478S-1483S.
10. Wagner TF, Drews A, Loch S, Mohr F, Philipp SE, Lambert S, Oberwinkler J. TRPM3 channels provide a regulated influx pathway for zinc in pancreatic beta cells. Pflugers Arch 2010. 460:755-765.
11. Lemaire K, Ravier MA, Schraenen A, Creemers JW, Van de Plas R, Granvik M, Van Lommel L, Waelkens E, Chimienti F, Rutter GA, et al. Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice. Proc Natl Acad Sci U S A 2009. 106:14872-14877.
12. Chimienti F, Devergnas S, Favier A, Seve M. Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules. Diabetes 2004. 53:2330-2337.
13. Gyulkhandanyan AV, Lu H, Lee SC, Bhattacharjee A, Wijesekara N, Fox JE, MacDonald PE, Chimienti F, Dai FF, Wheeler MB. Investigation of transport mechanisms and regulation of intracellular Zn2+ in pancreatic alpha-cells. J Biol Chem 2008. 283:10184-10197.
14. Dunn MF. Zinc-ligand interactions modulate assembly and stability of the insulin hexamer a review. BioMetals 2005. 18:295-303.
15. Faure P, Roussel AM, Martinie M, Osman M, Favier A, Halimi S. Insulin sensitivity in zinc-depleted rats: assessment with the euglycaemic hyperinsulinic clamp technique. Diabetes Metab 1991. 17:325-331.
16. Chen MD, Liou SJ, Lin PY, Yang VC, Alexander PS, Lin WH. Effects of zinc supplementation on the plasma glucose level and insulin activity in genetically obese (ob/ob) mice. Biol Trace Elem Res 1998. 61:303-311.
17. Qian WJ, Aspinwall CA, Battiste MA, Kennedy RT. Detection of secretion from single pancreatic beta-cells using extracellular fluorogenic reactions and confocal fluorescence microscopy. Anal Chem 2000. 72:711-717.
18. Kambe T, Narita H, Yamaguchi-Iwai Y, Hirose J, Amano T, Sugiura N, Sasaki R, Mori K, Iwanaga T, Nagao M. Cloning and characterization of a novel mammalian zinc transporter, zinc transporter 5, abundantly expressed in pancreatic beta cells. J Biol Chem 2002. 277:19049-19055.
19. Taylor KM, Vichova P, Jordan N, Hiscox S, Hendley R, Nicholson RI. ZIP7-mediated intracellular zinc transport contributes to aberrant growth factor signaling in antihormone-resistant breast cancer cells. Endocrinology 2008. 149:4912-4920.
20. MacDiarmid CW, Gaither LA, Eide D. Zinc transporters that regulate vacuolar zinc storage in Saccharomyces cerevisiae. EMBO J 2000. 19:2845-2855.
21. Huang L, Kirschke CP, Gitschier J. Functional characterization of a novel mammalian zinc transporter, ZnT6. J Biol Chem 2002. 277:26389-26395.
22. Cragg RA, Christie GR, Phillips SR, Russi RM, Küry S, Mathers JC, Taylor PM, Ford D. A novel zinc-regulated human zinc transporter, hZTL1, is localized to the enterocyte apical membrane. J Biol Chem 2002. 277:22789-22797.
23. Huang L, Gitschier J. A novel gene involved in zinc transport is deficient in the lethal milk mouse. Nat Genet 1997. 17:292-297.
24. Lopez V, Kelleher SL. Zinc transporter-2 (ZnT2) variants are localized to distinct subcellular compartments and functionally transport zinc. Biochem J 2009. 422:43-52.
25. Higgins TL, Murray M, Kett DH, Fulda G, Kramer KM, Gelmont D, Dedhia HV, Levy H, Teres D, Zaloga GP, Ko H, Thompson KA. Trace element homeostasis during continuous sedation with propofol containing EDTA versus other sedatives in critically ill patients. Intensive Care Med 2000. 26(Suppl 4): S413-S421.
26. Drogemuller C, Mohanasundaram DM, Murgia C, Mee C, Milner CR, Lang CJ, Zalewski PD, Haw-thorne W, Loudovaris T, Russ GR, Coates PT. Transcriptome analysis of isolated human pancreatic islets: expression profiles of zinc transporter genes in particular ZnT8 and ZIP14, critical islet marker genes and glucose metabolic genes. Xenotranspantation 2009. 16:5.
27. Rother KI, Harlan DM. Challenges facing islet transplantation for the treatment of type 1 diabetes mellitus. J Clin Invest 2004. 114:877-883.
28. Papas KK, Colton CK, Nelson RA, Rozak PR, Av-goustiniatos ES, Scott WE 3rd, Wildey GM, Pisania A, Weir GC, Hering BJ. Human islet oxygen consumption rate and DNA measurements predict diabetes reversal in nude mice. Am J Transplant 2007. 7:707-713.
29. Takahashi H, Tran PO, LeRoy E, Harmon JS, Ta-naka Y, Robertson RP. D-glyceraldehyde causes production of intracellular peroxide in pancreatic islets, oxidative stress, and defective beta cell function via non-mitochondrial pathways. J Biol Chem 2004. 279:37316-37323.
30. Li N, Brun T, Cnop M, Cunha DA, Eizirik DL, Maechler P. Transient oxidative stress damages mitochondrial machinery inducing persistent beta-cell dysfunction. J Biol Chem 2009. 284:23602-23612.
31. Wang H, Kouri G, Wollheim CB. ER stress and SREBP-1 activation are implicated in beta-cell glucolipo toxicity. J Cell Sci 2005. 118:3905-3915.
32. Lupi R, Del Guerra S, Mancarella R, Novelli M, Val-gimigli L, Pedulli GF, Paolini M, Soleti A, Filipponi F, Mosca F, Boggi U, Del Prato S, Masiello P, Marchetti P. Insulin secretion defects of human type 2 diabetic islets are corrected in vitro by a new reactive oxygen species scavenger. Diabetes Metab 2007. 33:340-345.
33. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Are oxidative stress-activated signaling pathways mediators of insulin resistance and beta-cell dysfunction? Diabetes 2003. 52:1-8.
34. Tang C, Han P, Oprescu AI, Lee SC, Gyulkhandan-yan AV, Chan GN, Wheeler MB, Giacca A. Evidence for a role of superoxide generation in glucose-induced betacell dysfunction in vivo. Diabetes 2007. 56:2722-2731.
35. Mohseni Salehi Monfared SS, Larijani B, Abdollahi M. Islet transplantation and antioxidant management: a comprehensive review. World J Gastroenterol 2009. 15:11531161.
36. Fontaine MJ, Fan W. Islet cell transplantation as a cure for insulin dependent diabetes: current improvements in preserving islet cell mass and function. Hepatobiliary Pancreat Dis Int 2003. 2:170-179.
37. Robertson RP. Oxidative stress and impaired insulin secretion in type 2 diabetes. Curr Opin Pharmacol 2006. 6:615-619.
38. Lenzen S, Drinkgern J, Tiedge M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic Biol Med 1996. 20:463-466.
39. Blostein-Fujii A, DiSilvestro R, Frid D, Katz C, Malarkey W. Short-term zinc supplementation in women with non-insulin-dependent diabetes mellitus: effects on plasma 5'-nucleotidase activities, insulin-like growth factor I concentrations, and lipoprotein oxidation rates in vitro. Am J Clin Nutr 1997. 66:639-642.
40. Zago MP, Oteiza PI. The antioxidant properties of zinc: interactions with iron and antioxidants. Free Radic Biol Med 2001. 31:266-274.
41. Bolkent S, Yanardag R, Mutlu O. The influence of zinc supplementation on the pancreas of streptozotocin-diabetic rats. Dig Dis Sci 2009. 54(12):2583-2587.
42. Yoshikawa Y, Ueda E, Kojima Y, Sakurai H. The action mechanism of zinc(II) complexes with insulinomimetic activity in rat adipocytes. Life Sci 2004. 75:741-751.
43. Coudray C, Richard MJ, Laporte F, Faure P, Roussel AM, Favier A. Superoxide dismutase activity and zinc status: a study in animals and man. J Nutr Environ Med 1992. 3:13-26.
44. Parham M, Amini M, Aminorroaya A, Heidarian E. Effect of zinc supplementation on microalbuminuria in patients with type 2 diabetes: a double blind, randomized, placebo-controlled, cross-over trial. Rev Diabet Stud 2008. 5(2):102-109.
45. You ZL, Shi DH, Zhu HL. The inhibition of xanthine oxidase by the schiff base zinc (II) complex. Inorg Chem Commun 2006. 9:642-644.
46. Roussel AM, Kerkeni A, Zouari N, Mahjoub S, Matheau JM, Anderson RA. Antioxidant effects of zinc supplementation in Tunisians with type 2 diabetes mellitus. J Am Coll Nutr 2003. 22:316-321.
47. Ryan MJ, Jackson JR, Hao Y, Leonard SS, Alway SE. Inhibition of xanthine oxidase reduces oxidative stress and improves skeletal muscle function in response to electrically stimulated isometric contractions in aged mice. Free Radic Biol Med 2010.
48. Ohly P, Dohle C, Abel J, Seissler J, Gleichmann H. Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin. Diabetologia 2000. 43:1020-1030.
49. Bettger WJ. Zinc and selenium, site-specific versus general antioxidation. Can J Physiol Pharmacol 1993. 71:721-724.
50. Verhaegh GW, Parat MO, Richard MJ, Hainaut P. Modulation of p53 protein conformation and DNA-binding activity by intracellular chelation of zinc. Mol Carcinog 1998. 21:205-214.
51. Emamaullee JA, Shapiro AM. Interventional strategies to prevent beta-cell apoptosis in islet transplantation. Diabetes 2006. 55:1907-1914.
52. Hughes A, Jessup C, Drogemuller C, Mohanasunda-ram D, Milner C, Rojas D, Russ GR, Coates PT. Gene therapy to improve pancreatic islet transplantation for type 1 diabetes mellitus. Curr Diabetes Rev 2010. 6(5):274-284.
53. Li X, Zhang L, Meshinchi S, Dias-Leme C, Raffin D, Johnson JD, Treutelaar MK, Burant CF. Islet microvasculature in islet hyperplasia and failure in a model of type 2 diabetes. Diabetes 2006. 55:2965-2973.
54. Chang KL, Hung TC, Hsieh BS, Chen YH, Chen TF, Cheng HL. Zinc at pharmacologic concentrations affects cytokine expression and induces apoptosis of human peripheral blood mononuclear cells. Nutrition 2006. 22(5):465-474.
55. Bao B, Prasad AS, Beck FW, Godmere M. Zinc modulates mRNA levels of cytokines. Am J Physiol Endocrinol Metab 2003. 285:E1095-E1102.
56. Prasad AS, Bao B, Beck FW, Kucuk O, Sarkar FH. Antioxidant effect of zinc in humans. Free Radic Biol Med 2004. 37:1182-1190.
57. Prasad AS, Bao B, Beck FW, Sarkar FH. Zinc-suppressed inflammatory cytokines by induction of A20-mediated inhibition of nuclear factor-kappaB. Nutrition 2010.
58. Tewari M, Wolf F, Seldin M, O'Shea K, Dixit V, Turka L. Lymphoid expression and regulation of A20, an inhibitor of programmed cell death. J Immunol 1995. 154:1699-1706.
59. Heyninck K, Beyaert R. The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappa B activation at the level of TRAF6. FEBS Lett 1999. 442:147-150.
60. Cooper JT, Stroka DM, Brostjan C, Palmetshofer A, Bach FH, Ferran C. A20 blocks endothelial cell activation through a NF-kappaB-dependent mechanism. J Biol Chem 1996. 271:18068-18073.
61. Falchuk KH. The molecular basis for the role of zinc in developmental biology. Mol Cell Biochem 1998. 188:41-48.
62. Dufner-Beattie J, Kuo YM, Gitschier J, Andrews GK. The adaptive response to dietary zinc in mice involves the differential cellular localization and zinc regulation of the zinc transporters ZIP4 and ZIP5. J Biol Chem 2004. 279:49082-49090.
63. Moynahan EJ. Acrodermatitis enteropathica: a lethal inherited human zinc-deficiency disorder. Lancet 1974. 2:399-400.
64. Neldner KH, Hambidge KM. Zinc therapy of acroder-matitis enteropathica. N Engl J Med 1975. 292:879-882.
65. McClain CJ. The pancreas and zinc homeostasis. J Lab Clin Med 1990. 116:275-276.
66. Hambidge M, Krebs NF. Interrelationships of key variables of human zinc homeostasis: relevance to dietary zinc requirements. Annu Rev Nutr 2001. 21:429-452.
67. Liuzzi JP, Bobo JA, Lichten LA, Samuelson DA, Cousins RJ. Responsive transporter genes within the murine intestinal-pancreatic axis form a basis of zinc homeostasis. Proc Natl Acad Sci U S A 2004. 101:14355-14360.
68. Zheng D, Feeney GP, Kille P, Hogstrand C. Regulation of ZIP and ZnT zinc transporters in zebrafish gill: zinc repression of ZIP10 transcription by an intronic MRE cluster. Physiol Genomics 2008. 34:205-214.
69. Achenbach P, Lampasona V, Landherr U, Koczwara K, Krause S, Grallert H, Winkler C, Pfluger M, Illig T, Bonifacio E, Ziegler AG. Autoantibodies to zinc transporter 8 and SLC30A8 genotype stratify type 1 diabetes risk. Diabetologia 2009. 52:1881-1888.
70. Huang L, Kirschke CP, Zhang Y, Yu YY. The ZIP7 gene (Slc39a7) encodes a zinc transporter involved in zinc homeostasis of the Golgi apparatus. J Biol Chem 2005. 280:15456-15463.
71. Guo L, Cousins RJ. ZnT1 (SLC30A1) and ZnT2 (SLC30A2) regulate zinc efflux through two different path-ways in pancreatic acinar cells. FASEB J 2008. 22:674.
72. Clifford KS, MacDonald MJ. Survey of mRNAs encoding zinc transporters and other metal complexing proteins in pancreatic islets of rats from birth to adulthood: similar patterns in the Sprague-Dawley and Wistar BB strains. Diabetes Res Clin Pract 2000. 49:77-85.
73. Smidt K, Jessen N, Petersen AB, Larsen A, Magnus-son N, Jeppesen JB, Stoltenberg M, Culvenor JG, Tsatsanis A, Brock B, 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:e5684.
74. Petersen AB, Smidt K, Magnusson NE, Moore F, Egefjord L, Rungby J. siRNA-mediated knock-down of ZnT3 and ZnT8 affects production and secretion of insulin and apoptosis in INS-1E cells. APMIS 2011.
75. Dufner-Beattie J, Langmade SJ, Wang F, Eide D, Andrews GK. Structure, function, and regulation of a subfamily of mouse zinc transporter genes. J Biol Chem 2003. 278:50142-50150.
76. Huang L, Yan M, Kirschke CP. Over-expression of ZnT7 increases insulin synthesis and secretion in pancreatic [beta]-cells by promoting insulin gene transcription. Exp Cell Res 2010. 316:2630-2643.
77. Chi ZH, Ren H, Wang X, Rong M, Huang L, Wang ZY. The cellular and subcellular localization of zinc transporter 7 in the mouse spinal cord. Histol Histopathol 2008. 23:781-787.
78. Chi ZH, Wang X, Wang ZY, Gao HL, Dahlstrom A, Huang L. Zinc transporter 7 is located in the cis-Golgi apparatus of mouse choroid epithelial cells. NeuroReport 2006. 17:1807-1811.
79. Kirschke CP, Huang L. ZnT7, a novel mammalian zinc transporter, accumulates zinc in the golgi apparatus. J Biol Chem 2003. 278:4096-4102.
80. Huang L, Yu YY, Kirschke CP, Gertz ER, Lloyd KK. Znt7 (Slc30a7)-deficient mice display reduced body zinc status and body fat accumulation. J Biol Chem 2007. 282:37053-37063.
81. Chimienti F, Favier A, Seve M. ZnT-8, a pancreatic beta-cell-specific zinc transporter. BioMetals 2005. 18:313-317.
82. Chimienti F, Devergnas S, Pattou F, Schuit F, Garcia-Cuenca R, Vandewalle B, Kerr-Conte J, Van Lommel L, Grunwald D, Favier A, Seve M. In vivo expression and functional characterization of the zinc transporter ZnT8 in glucose-induced insulin secretion. J Cell Sci 2006. 119:4199-4206.
83. Asfari M, Janjic D, Meda P, Li G, Halban P, Wollheim C. Establishment of 2-mercaptoethanol-dependent differentiated insulinsecreting cell lines. Endocrinology 1992. 130:167-178.
84. Smidt K, Pedersen SB, Brock B, Schmitz O, Fisker S, Bendix J, Wogensen L, Rungby J. Zinc-transporter genes in human visceral and subcutaneous adipocytes: Lean versus obese. Mol Cell Endocrinol 2007. 264:68-73.
85. Cauchi S, Del Guerra S, Choquet H, D'Aleo V, Groves CJ, Lupi R, McCarthy MI, Froguel P, Marchetti P. Meta-analysis and functional effects of the SLC30A8 rs13266634 polymorphism on isolated human pancreatic islets. Mol Genet Metab 2010. 100:77-82.
86. El Muayed M, Billings L, Raja M, Zhang X, Park P, Newman M, Kaufmen D, O'Halloran T, Lowe WL. Acute cytokine mediated downregulation of the zinc transporter ZnT8 alters pancreatic beta cell function. J Endocrinol 2010. 206(2):159-169.
87. Huang XF, Arvan P. Intracellular transport of proinsulin in pancreatic beta-cells. Structural maturation probed by disulfide accessibility. J Biol Chem 1995. 270:20417-20423.
88. Nicolson TJ, Bellomo EA, Wijesekara N, Loder MK, Baldwin JM, Gyulkhandanyan AV, Koshkin V, Tarasov AI, Carzaniga R, Kronenberger K, et al. Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetesassociated variants. Diabetes 2009. 58:2070-2083.
89. Pound LD, Sarkar SA, Benninger RKP, Wang Y, Suwanichkul A, Shadoan MK, Printz RL, Oeser JK, Lee CE, Piston DW, McGuinness OP, Hutton JC, Powell DR, O'Brien RM. Deletion of the mouse Slc30a8 gene encoding zinc transporter-8 results in impaired insulin secretion. Biochem J 2009. 421:371-376.
90. Kim I, Kang ES, Yim YS, Ko SJ, Jeong SH, Rim JH, Kim YS, Ahn CW, Cha BS, Lee HC, Kim CH. A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion. Pharmacogenomics J 2010.
91. Fu Y, Tian W, Pratt EB, Dirling LB, Shyng SL, Meshul CK, Cohen DM. Down-regulation of ZnT8 expression in INS-1 rat pancreatic beta cells reduces insulin content and glucose-inducible insulin secretion. PLoS One 2009. 4:e5679.
92. Wenzlau JM, Liu Y, Yu L, Moua O, Fowler KT, Rangasamy S, Walters J, Eisenbarth GS, Davidson HW, Hutton JC. A Common Nonsynonymous Single Nucleotide Polymorphism in the SLC30A8 Gene Determines ZnT8 Autoantibody Specificity in Type 1 Diabetes. Diabetes 2008. 57:2693-2697.
93. Wijesekara N, Dai F, Hardy A, Giglou P, Bhattacharjee A, Koshkin V, Chimienti F, Gaisano H, Rutter G, Wheeler M. Beta cell-specific Znt8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia 2010. 53(8):1656-1668.
94. Wenzlau JM, Moua O, Liu Y, Eisenbarth GS, Hutton JC, Davidson HW. Identification of a major humoral epitope in Slc30A8 (ZnT8). Ann N Y Acad Sci 2008. 1150:252-255
95. Wenzlau JM, Juhl K, Yu L, Moua O, Sarkar SA, Gottlieb P, Rewers M, Eisenbarth GS, Jensen J, Davidson HW, Hutton JC. The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A 2007. 104:17040-17045.
96. Gohlke H, Ferrari U, Koczwara K, Bonifacio E, Illig T, Ziegler AG. SLC30A8 (ZnT8) Polymorphism is Associated with Young Age at Type 1 Diabetes Onset. Rev Diabet Stud 2008. 5:25-27.
97. Vaziri-Sani F, Oak S, Radtke J, Lernmark K, Lynch K, Agardh CD, Cilio CM, Lethagen AL, Ortqvist E, Landin-Olsson M, Torn C, Hampe CS. ZnT8 auto antibody titers in type 1 diabetes patients decline rapidly after clinical onset. Autoimmunity 2010. 43:598-606.
98. Yan H, Yuan W, Velculescu VE, Vogelstein B, Kinzler KW. Allelic variation in human gene expression. Science 2002. 297:1143.
99. Lo HS, Wang Z, Hu Y, Yang HH, Gere S, Buetow KH, Lee MP. Allelic variation in gene expression is common in the human genome. Genome Res 2003. 13:1855-1862.
100. Sladek R, Rocheleau G, Rung J, Dina C, Shen L, Serre D, Boutin P, Vincent D, Belisle A, Hadjadj S, et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 2007. 445:881-885.
101. Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 2007. 316:1331-1336.
102. Scott LJ, Mohlke KL, Bonnycastle LL, Willer CJ, Li Y, Duren WL, Erdos MR, Stringham HM, Chines PS, Jackson AU, et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 2007. 316:1341-1345.
103. Steinthorsdottir V, Thorleifsson G, Reynisdottir I, Benediktsson R, Jonsdottir T, Walters GB, Styrkarsdottir U, Gretarsdottir S, Emilsson V, Ghosh S, et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nat Genet 2007. 39:770-775.
104. Staiger H, Machicao F, Stefan N, Tschritter O, Thamer C, Kantartzis K, Schäfer SA, Kirchhoff K, Fritsche A, Häring HU. Polymorphisms within novel risk loci for type 2 diabetes determine beta-cell function. PLoS One 2007. 2:e832.
105. Palmer ND, Goodarzi MO, Langefeld CD, Ziegler J, Norris JM, Haffner SM, Bryer-Ash M, Bergman RN, Wagenknecht LE, Taylor KD, Rotter JI, Bowden DW. Quantitative trait analysis of type 2 diabetes susceptibility loci identified from whole genome association studies in the insulin resistance atherosclerosis family study. Diabetes 2008. 57:1093-1100.
106. Xiang J, Li XY, Xu M, Hong J, Huang Y, Tan JR, Lu X, Dai M, Yu B, Ning G. Zinc transporter-8 gene (SLC30A8) is associated with type 2 diabetes in Chinese. J Clin Endocrinol Metab 2008. 93:4107-4112.
107. Pascoe L, Tura A, Patel SK, Ibrahim IM, Ferrannini E, Zeggini E, Weedon MN, Mari A, Hattersley AT, McCarthy MI, Frayling TM, Walker M. Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic betacell function. Diabetes 2007. 56:3101-3104.
108. Weijers R. Three-dimensional structure of beta-cellspecific zinc transporter, ZnT-8, predicted from the type 2 diabetes-associated gene variant SLC30A8 R325W. Diabetol Metab Syndr 2010. 2:33.
109. Hertel J, Johansson S, Ræder H, Midthjell K, Lyssenko V, Groop L, Molven A, Njølstad P. Genetic analysis of recently identified type 2 diabetes loci in 1,638 unselected patients with type 2 diabetes and 1,858 control participants from a Norwegian population-based cohort (the HUNT study). Diabetologia 2008. 51:971-977.
110. Kang ES, Kim MS, Kim YS, Kim CH, Han SJ, Chun SW, Hur KY, Nam CM, Ahn CW, Cha BS, Kim SI, Lee HC. A polymorphism in the zinc transporter gene SLC30A8 confers resistance against posttransplantation diabetes mellitus in renal allograft recipients. Diabetes 2008. 57:1043-1047