{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:23:42Z","timestamp":1791923022849,"version":"4.3.4"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2014,10,7]],"date-time":"2014-10-07T00:00:00Z","timestamp":1412640000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2015,1]]},"DOI":"10.1007\/s00125-014-3405-7","type":"journal-article","created":{"date-parts":[[2014,10,6]],"date-time":"2014-10-06T05:16:51Z","timestamp":1412572611000},"page":"31-36","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["SLC30A8 mutations in type 2 diabetes"],"prefix":"10.1007","volume":"58","author":[{"given":"Guy A.","family":"Rutter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Chimienti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,10,7]]},"reference":[{"key":"3405_CR1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.3945\/an.112.003038","volume":"4","author":"W Maret","year":"2013","unstructured":"Maret W (2013) Zinc biochemistry: from a single zinc enzyme to a key element of life. Adv Nutr 4:82\u201391","journal-title":"Adv Nutr"},{"key":"3405_CR2","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/S0959-440X(98)80037-7","volume":"8","author":"G Dodson","year":"1998","unstructured":"Dodson G, Steiner D (1998) The role of assembly in insulin\u2019s biosynthesis. Curr Opin Struct Biol 8:189\u2013194","journal-title":"Curr Opin Struct Biol"},{"key":"3405_CR3","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1007\/BF00275265","volume":"19","author":"SO Emdin","year":"1980","unstructured":"Emdin SO, Dodson GG, Cutfield JM, Cutfield SM (1980) Role of zinc in insulin biosynthesis. Some possible zinc-insulin interactions in the pancreatic B cell. Diabetologia 19:174\u2013182","journal-title":"Diabetologia"},{"key":"3405_CR4","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1042\/bj2100297","volume":"210","author":"JC Hutton","year":"1983","unstructured":"Hutton JC, Penn EJ, Peshavaria M (1983) Low-molecular-weight constituents of isolated insulin-secretory vesicles. Bivalent cations, adenine nucleotides and inorganic phosphate. Biochem J 210:297\u2013305","journal-title":"Biochem J"},{"key":"3405_CR5","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nmeth.1368","volume":"6","author":"JL Vinkenborg","year":"2009","unstructured":"Vinkenborg JL, Nicolson TJ, Bellomo EA, Koay MS, Rutter GA, Merkx M (2009) Genetically encoded FRET sensors to monitor intracellular Zn2+ homeostasis. Nat Methods 6:737\u2013740","journal-title":"Nat Methods"},{"key":"3405_CR6","doi-asserted-by":"crossref","first-page":"8943","DOI":"10.1073\/pnas.85.23.8943","volume":"85","author":"RJ Carroll","year":"1988","unstructured":"Carroll RJ, Hammer RE, Chan SJ, Swift HH, Rubenstein AH, Steiner DF (1988) A mutant human proinsulin is secreted from islets of Langerhans in increased amounts via an unregulated pathway. Proc Natl Acad Sci U S A 85:8943\u20138947","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3405_CR7","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1080\/07315724.1998.10718735","volume":"17","author":"AB Chausmer","year":"1998","unstructured":"Chausmer AB (1998) Zinc, insulin and diabetes. J Am Coll Nutr 17:109\u2013115","journal-title":"J Am Coll Nutr"},{"key":"3405_CR8","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/nature05616","volume":"445","author":"R Sladek","year":"2007","unstructured":"Sladek R, Rocheleau G, Rung J et al (2007) A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445:881\u2013885","journal-title":"Nature"},{"key":"3405_CR9","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.2337\/diabetes.53.9.2330","volume":"53","author":"F Chimienti","year":"2004","unstructured":"Chimienti F, Devergnas S, Favier A, Seve M (2004) Identification and cloning of a beta-cell-specific zinc transporter, ZnT-8, localized into insulin secretory granules. Diabetes 53:2330\u20132337","journal-title":"Diabetes"},{"key":"3405_CR10","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1146\/annurev-nutr-033009-083312","volume":"29","author":"LA Lichten","year":"2009","unstructured":"Lichten LA, Cousins RJ (2009) Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev Nutr 29:153\u2013176","journal-title":"Annu Rev Nutr"},{"key":"3405_CR11","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1007\/s00125-014-3266-0","volume":"57","author":"PA Gerber","year":"2014","unstructured":"Gerber PA, Bellomo EA, Hodson DJ et al (2014) Hypoxia lowers SLC30A8\/ZnT8 expression and free cytosolic Zn2+ in pancreatic beta cells. Diabetologia 57:1635\u20131644","journal-title":"Diabetologia"},{"key":"3405_CR12","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1007\/s00125-008-0955-6","volume":"51","author":"TW Boesgaard","year":"2008","unstructured":"Boesgaard TW, Zilinskaite J, Vanttinen M et al (2008) 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 51:816\u2013820","journal-title":"Diabetologia"},{"key":"3405_CR13","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ymgme.2010.01.001","volume":"100","author":"S Cauchi","year":"2010","unstructured":"Cauchi S, Del GS, Choquet H et al (2010) Meta-analysis and functional effects of the SLC30A8 rs13266634 polymorphism on isolated human pancreatic islets. Mol Genet Metab 100:77\u201382","journal-title":"Mol Genet Metab"},{"key":"3405_CR14","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1007\/s00125-008-0926-y","volume":"51","author":"K Kirchhoff","year":"2008","unstructured":"Kirchhoff K, Machicao F, Haupt A et al (2008) Polymorphisms in the TCF7L2, CDKAL1 and SLC30A8 genes are associated with impaired proinsulin conversion. Diabetologia 51:597\u2013601","journal-title":"Diabetologia"},{"key":"3405_CR15","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.2337\/db09-0551","volume":"58","author":"TJ Nicolson","year":"2009","unstructured":"Nicolson TJ, Bellomo EA, Wijesekara N et al (2009) Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes-associated variants. Diabetes 58:2070\u20132083","journal-title":"Diabetes"},{"key":"3405_CR16","doi-asserted-by":"crossref","first-page":"14872","DOI":"10.1073\/pnas.0906587106","volume":"106","author":"K Lemaire","year":"2009","unstructured":"Lemaire K, Ravier MA, Schraenen A et al (2009) 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 106:14872\u201314877","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3405_CR17","doi-asserted-by":"crossref","first-page":"4513","DOI":"10.1172\/JCI68807","volume":"123","author":"M Tamaki","year":"2013","unstructured":"Tamaki M, Fujitani Y, Hara A et al (2013) The diabetes-susceptible gene SLC30A8\/ZnT8 regulates hepatic insulin clearance. J Clin Invest 123:4513\u20134524","journal-title":"J Clin Invest"},{"key":"3405_CR18","doi-asserted-by":"crossref","first-page":"17040","DOI":"10.1073\/pnas.0705894104","volume":"104","author":"JM Wenzlau","year":"2007","unstructured":"Wenzlau JM, Juhl K, Yu L et al (2007) The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A 104:17040\u201317045","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3405_CR19","doi-asserted-by":"crossref","unstructured":"Wenzlau JM, Moua O, Sarkar SA et al (2008) SlC30A8 is a major target of humoral autoimmunity in type 1 diabetes and a predictive marker in prediabetes. Ann N Y Acad Sci 1150:256\u2013259","DOI":"10.1196\/annals.1447.029"},{"key":"3405_CR20","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-5996-2-33","volume":"2","author":"RN Weijers","year":"2010","unstructured":"Weijers RN (2010) Three-dimensional structure of beta-cell-specific zinc transporter, ZnT-8, predicted from the type 2 diabetes-associated gene variant SLC30A8 R325W. Diabetol Metab Syndr 2:33","journal-title":"Diabetol Metab Syndr"},{"key":"3405_CR21","doi-asserted-by":"crossref","first-page":"17173","DOI":"10.1074\/jbc.M400208200","volume":"279","author":"Y Chao","year":"2004","unstructured":"Chao Y, Fu D (2004) Thermodynamic studies of the mechanism of metal binding to the Escherichia coli zinc transporter YiiP. J Biol Chem 279:17173\u201317180","journal-title":"J Biol Chem"},{"key":"3405_CR22","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/tpj.2010.22","volume":"11","author":"I Kim","year":"2010","unstructured":"Kim I, Kang ES, Yim YS et al (2010) A low-risk ZnT-8 allele (W325) for post-transplantation diabetes mellitus is protective against cyclosporin A-induced impairment of insulin secretion. Pharmacogenomics J 11:191\u2013198","journal-title":"Pharmacogenomics J"},{"key":"3405_CR23","doi-asserted-by":"crossref","unstructured":"Davidson HW, Wenzlau JM, O\u2019Brien RM (2014) Zinc transporter 8 (ZnT8) and beta cell function. Trends Endocrinol Metab 25:415\u2013424","DOI":"10.1016\/j.tem.2014.03.008"},{"key":"3405_CR24","doi-asserted-by":"crossref","first-page":"14389","DOI":"10.1074\/jbc.M701752200","volume":"282","author":"RA Valentine","year":"2007","unstructured":"Valentine RA, Jackson KA, Christie GR, Mathers JC, Taylor PM, Ford D (2007) ZnT5 variant B is a bidirectional zinc transporter and mediates zinc uptake in human intestinal Caco-2 cells. J Biol Chem 282:14389\u201314393","journal-title":"J Biol Chem"},{"key":"3405_CR25","doi-asserted-by":"crossref","first-page":"7202","DOI":"10.1073\/pnas.1200362109","volume":"109","author":"E Hoch","year":"2012","unstructured":"Hoch E, Lin W, Chai J, Hershfinkel M, Fu D, Sekler I (2012) Histidine pairing at the metal transport site of mammalian ZnT transporters controls Zn2+ over Cd2+ selectivity. Proc Natl Acad Sci U S A 109:7202\u20137207","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3405_CR26","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1042\/BJ20090530","volume":"421","author":"LD Pound","year":"2009","unstructured":"Pound LD, Sarkar SA, Benninger RK et al (2009) Deletion of the mouse Slc30a8 gene encoding zinc transporter-8 results in impaired insulin secretion. Biochem J 421:371\u2013376","journal-title":"Biochem J"},{"key":"3405_CR27","doi-asserted-by":"crossref","first-page":"e40972","DOI":"10.1371\/journal.pone.0040972","volume":"7","author":"LD Pound","year":"2012","unstructured":"Pound LD, Sarkar SA, Ustione A et al (2012) The physiological effects of deleting the mouse slc30a8 gene encoding zinc transporter-8 are influenced by gender and genetic background. PLoS One 7:e40972","journal-title":"PLoS One"},{"key":"3405_CR28","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1007\/s00125-010-1733-9","volume":"53","author":"N Wijesekara","year":"2010","unstructured":"Wijesekara N, Dai FF, Hardy AB et al (2010) Beta cell specific ZnT8 deletion in mice causes marked defects in insulin processing, crystallisation and secretion. Diabetologia 53:1656\u20131668","journal-title":"Diabetologia"},{"key":"3405_CR29","doi-asserted-by":"crossref","first-page":"E1084","DOI":"10.1152\/ajpendo.00448.2011","volume":"302","author":"AB Hardy","year":"2012","unstructured":"Hardy AB, Wijesekara N, Genkin I et al (2012) Effects of high-fat diet feeding on Znt8-null mice: differences between beta-cell and global knockout of Znt8. Am J Physiol Endocrinol Metab 302:E1084\u2013E1096","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"3405_CR30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4161\/isl.2.1.10259","volume":"2","author":"GA Rutter","year":"2010","unstructured":"Rutter GA (2010) Think zinc: new roles for zinc in the control of insulin secretion. Islets 2:1\u20132","journal-title":"Islets"},{"key":"3405_CR31","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/0006-291X(66)90785-6","volume":"25","author":"J Quarterman","year":"1966","unstructured":"Quarterman J, Mills CF, Humphries WR (1966) The reduced secretion of, and sensitivity to insulin in zinc-deficient rats. Biochem Biophys Res Commun 25:354\u2013358","journal-title":"Biochem Biophys Res Commun"},{"key":"3405_CR32","doi-asserted-by":"crossref","first-page":"665","DOI":"10.2337\/diab.29.8.665","volume":"29","author":"L Coulston","year":"1980","unstructured":"Coulston L, Dandona P (1980) Insulin-like effect of zinc on adipocytes. Diabetes 29:665\u2013667","journal-title":"Diabetes"},{"key":"3405_CR33","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s10534-005-3707-9","volume":"18","author":"H Haase","year":"2005","unstructured":"Haase H, Maret W (2005) Protein tyrosine phosphatases as targets of the combined insulinomimetic effects of zinc and oxidants. Biometals 18:333\u2013338","journal-title":"Biometals"},{"key":"3405_CR34","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/ng.2915","volume":"46","author":"J Flannick","year":"2014","unstructured":"Flannick J, Thorleifsson G, Beer NL et al (2014) Loss-of-function mutations in SLC30A8 protect against type 2 diabetes. Nat Genet 46:357\u2013363","journal-title":"Nat Genet"},{"key":"3405_CR35","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.2337\/db07-0761","volume":"57","author":"ES Kang","year":"2008","unstructured":"Kang ES, Kim MS, Kim YS et al (2008) A polymorphism in the zinc transporter gene SLC30A8 confers resistance against posttransplantation diabetes mellitus in renal allograft recipients. Diabetes 57:1043\u20131047","journal-title":"Diabetes"},{"key":"3405_CR36","doi-asserted-by":"crossref","first-page":"367","DOI":"10.2337\/diabetes.49.3.367","volume":"49","author":"BJ Kim","year":"2000","unstructured":"Kim BJ, Kim YH, Kim S et al (2000) Zinc as a paracrine effector in pancreatic islet cell death. Diabetes 49:367\u2013372","journal-title":"Diabetes"},{"key":"3405_CR37","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/S0891-5849(01)00701-8","volume":"31","author":"F Chimienti","year":"2001","unstructured":"Chimienti F, Jourdan E, Favier A, Seve M (2001) Zinc resistance impairs sensitivity to oxidative stress in HeLa cells: protection through metallothioneins expression. Free Radic Biol Med 31:1179\u20131190","journal-title":"Free Radic Biol Med"},{"key":"3405_CR38","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1126\/science.1142364","volume":"316","author":"E Zeggini","year":"2007","unstructured":"Zeggini E, Weedon MN, Lindgren CM et al (2007) Replication of genome-wide association signals in U.K. samples reveals risk loci for type 2 diabetes. Science 316:1336\u20131341","journal-title":"Science"},{"key":"3405_CR39","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1126\/science.1142382","volume":"316","author":"LJ Scott","year":"2007","unstructured":"Scott LJ, Mohlke KL, Bonnycastle LL et al (2007) A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316:1341\u20131345","journal-title":"Science"},{"key":"3405_CR40","doi-asserted-by":"crossref","first-page":"906590","DOI":"10.1155\/2013\/906590","volume":"2013","author":"G Silva Xavier da","year":"2013","unstructured":"da Silva Xavier G, Bellomo EA, McGinty JA, French PM, Rutter GA (2013) Animal models of GWAS-identified type 2 diabetes genes. J Diabetes Res 2013:906590","journal-title":"J Diabetes Res"},{"key":"3405_CR41","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1007\/s00125-009-1321-z","volume":"52","author":"SE Kahn","year":"2009","unstructured":"Kahn SE, Zraika S, Utzschneider KM, Hull RL (2009) The beta cell lesion in type 2 diabetes: there has to be a primary functional abnormality. Diabetologia 52:1003\u20131012","journal-title":"Diabetologia"},{"key":"3405_CR42","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.2337\/db08-0425","volume":"57","author":"M Hoek van","year":"2008","unstructured":"van Hoek M, Dehghan A, Witteman JC et al (2008) Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study. Diabetes 57:3122\u20133128","journal-title":"Diabetes"},{"key":"3405_CR43","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.2337\/db08-0504","volume":"57","author":"H Lango","year":"2008","unstructured":"Lango H, Palmer CN, Morris AD et al (2008) Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk. Diabetes 57:3129\u20133135","journal-title":"Diabetes"},{"key":"3405_CR44","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nm.3163","volume":"19","author":"Nature Medicine","year":"2013","unstructured":"Nature Medicine (2013) Of men, not mice. Nat Med 19:379","journal-title":"Nat Med"},{"key":"3405_CR45","doi-asserted-by":"crossref","first-page":"894","DOI":"10.2337\/db08-1187","volume":"58","author":"G Silva Xavier da","year":"2009","unstructured":"da Silva Xavier G, Loder MK, McDonald A et al (2009) TCF7L2 regulates late events in insulin secretion from pancreatic islet beta-cells. Diabetes 58:894\u2013905","journal-title":"Diabetes"},{"key":"3405_CR46","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1007\/s00125-012-2600-7","volume":"55","author":"G Silva Xavier da","year":"2012","unstructured":"da Silva Xavier G, Mondragon A, Sun G et al (2012) Abnormal glucose tolerance and insulin secretion in pancreas-specific Tcf7l2 null mice. Diabetologia 55:2667\u20132676","journal-title":"Diabetologia"},{"key":"3405_CR47","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1073\/pnas.0436428100","volume":"100","author":"CR White","year":"2003","unstructured":"White CR, Seymour RS (2003) Mammalian basal metabolic rate is proportional to body mass2\/3. Proc Natl Acad Sci U S A 100:4046\u20134049","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3405_CR48","doi-asserted-by":"crossref","first-page":"124","DOI":"10.4161\/isl.1.2.9433","volume":"1","author":"M Tamaki","year":"2009","unstructured":"Tamaki M, Fujitani Y, Uchida T, Hirose T, Kawamori R, Watada H (2009) Downregulation of ZnT8 expression in pancreatic beta-cells of diabetic mice. Islets 1:124\u2013128","journal-title":"Islets"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-014-3405-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00125-014-3405-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-014-3405-7","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T07:53:50Z","timestamp":1558598030000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00125-014-3405-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10,7]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["3405"],"URL":"https:\/\/doi.org\/10.1007\/s00125-014-3405-7","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,7]]}}}