{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:14:17Z","timestamp":1790648057630,"version":"4.1.0"},"reference-count":46,"publisher":"American Diabetes Association","issue":"2","license":[{"start":{"date-parts":[[2017,1,20]],"date-time":"2017-01-20T00:00:00Z","timestamp":1484870400000},"content-version":"vor","delay-in-days":51,"URL":"http:\/\/www.diabetesjournals.org\/content\/license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["81570338"],"award-info":[{"award-number":["81570338"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["81470975"],"award-info":[{"award-number":["81470975"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Science Foundation of China","doi-asserted-by":"crossref","award":["81270809"],"award-info":[{"award-number":["81270809"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Graduate Innovation Fund of Jilin University","award":["2015032"],"award-info":[{"award-number":["2015032"]}]},{"name":"Jilin University Bethune Foundation","award":["2012221"],"award-info":[{"award-number":["2012221"]}]},{"name":"Jilin Province Science and Technology Development Project","award":["20140519012JH"],"award-info":[{"award-number":["20140519012JH"]}]},{"DOI":"10.13039\/100000963","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1-13-JF-53"],"award-info":[{"award-number":["1-13-JF-53"]}],"id":[{"id":"10.13039\/100000963","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000963","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["1-15-BS-018"],"award-info":[{"award-number":["1-15-BS-018"]}],"id":[{"id":"10.13039\/100000963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,2,1]]},"abstract":"<jats:p>We have reported that sulforaphane (SFN) prevented diabetic cardiomyopathy in both type 1 and type 2 diabetes (T2DM) animal models via the upregulation of nuclear transcription factor erythroid 2\u2013related factor 2 (Nrf2) and metallothionein (MT). In this study, we tested whether SFN protects the heart from T2DM directly through Nrf2, MT, or both. Using Nrf2-knockout (KO), MT-KO, and wild-type (WT) mice, T2DM was induced by feeding a high-fat diet for 3 months followed by a small dose of streptozotocin. Age-matched controls were given a normal diet. Both T2DM and control mice were then treated with or without SFN for 4 months by continually feeding a high-fat or normal diet. SFN prevented diabetes-induced cardiac dysfunction as well as diabetes-associated cardiac oxidative damage, inflammation, fibrosis, and hypertrophy, with increases in Nrf2 and MT expressions in the WT mice. Both Nrf2-KO and MT-KO diabetic mice exhibited greater cardiac damage than WT diabetic mice. SFN did not provide cardiac protection in Nrf2-KO mice, but partially or completely protected the heart from diabetes in MT-KO mice. SFN did not induce MT expression in Nrf2-KO mice, but stimulated Nrf2 function in MT-KO mice. These results suggest that Nrf2 plays the indispensable role for SFN cardiac protection from T2DM with significant induction of MT and other antioxidants. MT expression induced by SFN is Nrf2 dependent, but is not indispensable for SFN-induced cardiac protection from T2DM.<\/jats:p>","DOI":"10.2337\/db15-1274","type":"journal-article","created":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T03:20:22Z","timestamp":1480562422000},"page":"529-542","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":183,"title":["Metallothionein Is Downstream of Nrf2 and Partially Mediates Sulforaphane Prevention of Diabetic Cardiomyopathy"],"prefix":"10.2337","volume":"66","author":[{"given":"Junlian","family":"Gu","sequence":"first","affiliation":[{"name":"The First Hospital of Jilin University, Changchun, Jilin, China"},{"name":"Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanli","family":"Cheng","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University, Changchun, Jilin, China"},{"name":"Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY"},{"name":"The Second Hospital of Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Kong","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University, Changchun, Jilin, China"},{"name":"Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shudong","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University, Changchun, Jilin, China"},{"name":"Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University, Changchun, Jilin, China"},{"name":"Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Tan","sequence":"additional","affiliation":[{"name":"Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY"},{"name":"Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley B.","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY"},{"name":"Kosair Charities Pediatric Heart Research Program, Cardiovascular Innovation Institute, University of Louisville, Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglan","family":"Zhou","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehui","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonggao","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University, Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Cai","sequence":"additional","affiliation":[{"name":"The First Hospital of Jilin University, Changchun, Jilin, China"},{"name":"Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China"},{"name":"Department of Pediatrics, Pediatric Research Institute, University of Louisville, Louisville, KY"},{"name":"Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2016,11,30]]},"reference":[{"key":"2022031300103482300_B1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.4093\/dmj.2014.38.5.337","article-title":"Diabetic cardiomyopathy and its prevention by nrf2: current status","volume":"38","author":"Chen","year":"2014","journal-title":"Diabetes Metab J"},{"key":"2022031300103482300_B2","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.freeradbiomed.2015.08.009","article-title":"Metallothionein plays a prominent role in the prevention of diabetic nephropathy by sulforaphane via up-regulation of Nrf2","volume":"89","author":"Wu","year":"2015","journal-title":"Free Radic Biol Med"},{"key":"2022031300103482300_B3","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/CIRCRESAHA.110.223545","article-title":"Oxidative stress and diabetic complications","volume":"107","author":"Giacco","year":"2010","journal-title":"Circ Res"},{"key":"2022031300103482300_B4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1385\/CT:1:3:181","article-title":"Oxidative stress and diabetic cardiomyopathy: a brief review","volume":"1","author":"Cai","year":"2001","journal-title":"Cardiovasc Toxicol"},{"key":"2022031300103482300_B5","doi-asserted-by":"crossref","first-page":"13291","DOI":"10.1074\/jbc.R900010200","article-title":"The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress","volume":"284","author":"Nguyen","year":"2009","journal-title":"J Biol Chem"},{"key":"2022031300103482300_B6","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.yjmcc.2013.01.008","article-title":"Prevention by sulforaphane of diabetic cardiomyopathy is associated with up-regulation of Nrf2 expression and transcription activation","volume":"57","author":"Bai","year":"2013","journal-title":"J Mol Cell Cardiol"},{"key":"2022031300103482300_B7","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.yjmcc.2014.09.022","article-title":"Sulforaphane prevents the development of cardiomyopathy in type 2 diabetic mice probably by reversing oxidative stress-induced inhibition of LKB1\/AMPK pathway","volume":"77","author":"Zhang","year":"2014","journal-title":"J Mol Cell Cardiol"},{"key":"2022031300103482300_B8","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.jacc.2006.07.022","article-title":"Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy","volume":"48","author":"Cai","year":"2006","journal-title":"J Am Coll Cardiol"},{"key":"2022031300103482300_B9","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1161\/CIRCULATIONAHA.105.537894","article-title":"Cardiac metallothionein induction plays the major role in the prevention of diabetic cardiomyopathy by zinc supplementation","volume":"113","author":"Wang","year":"2006","journal-title":"Circulation"},{"key":"2022031300103482300_B10","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.2337\/db08-1697","article-title":"Inactivation of GSK-3beta by metallothionein prevents diabetes-related changes in cardiac energy metabolism, inflammation, nitrosative damage, and remodeling","volume":"58","author":"Wang","year":"2009","journal-title":"Diabetes"},{"key":"2022031300103482300_B11","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.jnutbio.2008.12.010","article-title":"Zinc supplementation partially prevents renal pathological changes in diabetic rats","volume":"21","author":"Tang","year":"2010","journal-title":"J Nutr Biochem"},{"key":"2022031300103482300_B12","doi-asserted-by":"crossref","first-page":"e0138771","DOI":"10.1371\/journal.pone.0138771","article-title":"Sulforaphane protects the liver against CdSe quantum dot-induced cytotoxicity","volume":"10","author":"Wang","year":"2015","journal-title":"PLoS One"},{"key":"2022031300103482300_B13","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1124\/jpet.103.064261","article-title":"In vivo pharmacokinetics and regulation of gene expression profiles by isothiocyanate sulforaphane in the rat","volume":"310","author":"Hu","year":"2004","journal-title":"J Pharmacol Exp Ther"},{"key":"2022031300103482300_B14","doi-asserted-by":"crossref","first-page":"E14","DOI":"10.1152\/ajpendo.00702.2013","article-title":"Sulforaphane reduction of testicular apoptotic cell death in diabetic mice is associated with the upregulation of Nrf2 expression and function","volume":"307","author":"Wang","year":"2014","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2022031300103482300_B15","doi-asserted-by":"crossref","first-page":"10505","DOI":"10.1021\/jf801989e","article-title":"Bioavailability and kinetics of sulforaphane in humans after consumption of cooked versus raw broccoli","volume":"56","author":"Vermeulen","year":"2008","journal-title":"J Agric Food Chem"},{"key":"2022031300103482300_B16","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1017\/S0007114507824093","article-title":"Absolute bioavailability and dose-dependent pharmacokinetic behaviour of dietary doses of the chemopreventive isothiocyanate sulforaphane in rat","volume":"99","author":"Hanlon","year":"2008","journal-title":"Br J Nutr"},{"key":"2022031300103482300_B17","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.etp.2010.11.005","article-title":"Protective effect of sulforaphane against oxidative stress: recent advances","volume":"64","author":"Guerrero-Beltr\u00e1n","year":"2012","journal-title":"Exp Toxicol Pathol"},{"key":"2022031300103482300_B18","first-page":"821936","article-title":"Prevention of diabetic nephropathy by sulforaphane: possible role of nrf2 upregulation and activation","volume-title":"Oxid Med Cell Longev","author":"Cui","year":"2012"},{"key":"2022031300103482300_B19","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.taap.2014.06.009","article-title":"Protection by sulforaphane from type 1 diabetes-induced testicular apoptosis is associated with the up-regulation of Nrf2 expression and function","volume":"279","author":"Jiang","year":"2014","journal-title":"Toxicol Appl Pharmacol"},{"key":"2022031300103482300_B20","doi-asserted-by":"crossref","first-page":"F105","DOI":"10.1152\/ajprenal.00034.2013","article-title":"Metallothionein deficiency exacerbates diabetic nephropathy in streptozotocin-induced diabetic mice","volume":"306","author":"Tachibana","year":"2014","journal-title":"Am J Physiol Renal Physiol"},{"key":"2022031300103482300_B21","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s12011-014-9923-9","article-title":"Zinc supplementation alleviates diabetic peripheral neuropathy by inhibiting oxidative stress and upregulating metallothionein in peripheral nerves of diabetic rats","volume":"158","author":"Liu","year":"2014","journal-title":"Biol Trace Elem Res"},{"key":"2022031300103482300_B22","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1007\/s001250050009","article-title":"Zinc sulphate induces metallothionein in pancreatic islets of mice and protects against diabetes induced by multiple low doses of streptozotocin","volume":"43","author":"Ohly","year":"2000","journal-title":"Diabetologia"},{"key":"2022031300103482300_B23","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s13105-012-0174-y","article-title":"Effect of zinc supplementation on type 2 diabetes parameters and liver metallothionein expressions in Wistar rats","volume":"68","author":"Wang","year":"2012","journal-title":"J Physiol Biochem"},{"key":"2022031300103482300_B24","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1210\/en.2014-1619","article-title":"The protective effect of FGF21 on diabetes-induced male germ cell apoptosis is associated with up-regulated testicular AKT and AMPK\/Sirt1\/PGC-1\u03b1 signaling","volume":"156","author":"Jiang","year":"2015","journal-title":"Endocrinology"},{"key":"2022031300103482300_B25","first-page":"123963","article-title":"Sulforaphane attenuation of type 2 diabetes-induced aortic damage was associated with the upregulation of nrf2 expression and function","volume-title":"Oxid Med Cell Longev","author":"Wang","year":"2014"},{"key":"2022031300103482300_B26","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1016\/j.freeradbiomed.2008.02.013","article-title":"Zinc protects endothelial cells from hydrogen peroxide via Nrf2-dependent stimulation of glutathione biosynthesis","volume":"44","author":"Cortese","year":"2008","journal-title":"Free Radic Biol Med"},{"key":"2022031300103482300_B27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/1475-2840-12-54","article-title":"Zinc protects against diabetes-induced pathogenic changes in the aorta: roles of metallothionein and nuclear factor (erythroid-derived 2)-like 2","volume":"12","author":"Miao","year":"2013","journal-title":"Cardiovasc Diabetol"},{"key":"2022031300103482300_B28","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1111\/jcmm.12239","article-title":"Zinc is essential for the transcription function of Nrf2 in human renal tubule cells in vitro and mouse kidney in vivo under the diabetic condition","volume":"18","author":"Li","year":"2014","journal-title":"J Cell Mol Med"},{"key":"2022031300103482300_B29","first-page":"452","article-title":"Role of zinc supplementation in testicular and epididymal damages in diabetic rat: involvement of Nrf2, SOD1, and GPX5","volume-title":"Biol Trace Elem Res","author":"Maremanda","year":"2016"},{"key":"2022031300103482300_B30","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.nbt.2011.05.003","article-title":"Hepatoprotection of quercetin against oxidative stress by induction of metallothionein expression through activating MAPK and PI3K pathways and enhancing Nrf2 DNA-binding activity","volume":"28","author":"Weng","year":"2011","journal-title":"N Biotechnol"},{"key":"2022031300103482300_B31","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.taap.2016.01.020","article-title":"Partial contribution of the Keap1-Nrf2 system to cadmium-mediated metallothionein expression in vascular endothelial cells","volume":"295","author":"Shinkai","year":"2016","journal-title":"Toxicol Appl Pharmacol"},{"key":"2022031300103482300_B32","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.yjmcc.2008.10.007","article-title":"Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes","volume":"46","author":"He","year":"2009","journal-title":"J Mol Cell Cardiol"},{"key":"2022031300103482300_B33","doi-asserted-by":"crossref","first-page":"625","DOI":"10.2337\/db10-1164","article-title":"Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo","volume":"60","author":"Tan","year":"2011","journal-title":"Diabetes"},{"key":"2022031300103482300_B34","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s40618-014-0086-5","article-title":"Oscillating high glucose enhances oxidative stress and apoptosis in human coronary artery endothelial cells","volume":"37","author":"Liu","year":"2014","journal-title":"J Endocrinol Invest"},{"key":"2022031300103482300_B35","doi-asserted-by":"crossref","first-page":"20290","DOI":"10.3390\/ijms151120290","article-title":"Nrf2 and redox status in prediabetic and diabetic patients","volume":"15","author":"Jim\u00e9nez-Osorio","year":"2014","journal-title":"Int J Mol Sci"},{"key":"2022031300103482300_B36","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/ced.12487","article-title":"Increased protein oxidation and decreased expression of nuclear factor E2-related factor 2 protein in skin tissue of patients with diabetes","volume":"40","author":"Lee","year":"2015","journal-title":"Clin Exp Dermatol"},{"key":"2022031300103482300_B37","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1023\/A:1006966005662","article-title":"Alterations of proteasome activities in skeletal muscle tissue of diabetic rats","volume":"26","author":"Merforth","year":"1999","journal-title":"Mol Biol Rep"},{"key":"2022031300103482300_B38","doi-asserted-by":"crossref","first-page":"4160","DOI":"10.1210\/en.2006-0251","article-title":"Insulin resistance accelerates muscle protein degradation: Activation of the ubiquitin-proteasome pathway by defects in muscle cell signaling","volume":"147","author":"Wang","year":"2006","journal-title":"Endocrinology"},{"key":"2022031300103482300_B39","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.lfs.2010.12.023","article-title":"Prevention of diabetic nephropathy in rats through enhanced renal antioxidative capacity by inhibition of the proteasome","volume":"88","author":"Luo","year":"2011","journal-title":"Life Sci"},{"key":"2022031300103482300_B40","doi-asserted-by":"crossref","first-page":"E87","DOI":"10.1152\/ajpendo.00430.2012","article-title":"Potential role for Nrf2 activation in the therapeutic effect of MG132 on diabetic nephropathy in OVE26 diabetic mice","volume":"304","author":"Cui","year":"2013","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"2022031300103482300_B41","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1007\/s00395-014-0450-9","article-title":"Heme oxygenase-1: an emerging therapeutic target to curb cardiac pathology","volume":"109","author":"Czibik","year":"2014","journal-title":"Basic Res Cardiol"},{"key":"2022031300103482300_B42","doi-asserted-by":"crossref","first-page":"e92246","DOI":"10.1371\/journal.pone.0092246","article-title":"Heme oxygenase-1 induction improves cardiac function following myocardial ischemia by reducing oxidative stress","volume":"9","author":"Issan","year":"2014","journal-title":"PLoS One"},{"key":"2022031300103482300_B43","doi-asserted-by":"crossref","first-page":"e75927","DOI":"10.1371\/journal.pone.0075927","article-title":"Heme oxygenase-1 prevents cardiac dysfunction in streptozotocin-diabetic mice by reducing inflammation, oxidative stress, apoptosis and enhancing autophagy","volume":"8","author":"Zhao","year":"2013","journal-title":"PLoS One"},{"key":"2022031300103482300_B44","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.jnutbio.2014.12.008","article-title":"Sulforaphane attenuation of experimental diabetic nephropathy involves GSK-3 beta\/Fyn\/Nrf2 signaling pathway","volume":"26","author":"Shang","year":"2015","journal-title":"J Nutr Biochem"},{"key":"2022031300103482300_B45","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.freeradbiomed.2015.06.012","article-title":"Functional polymorphisms in Nrf2: implications for human disease","volume":"88","author":"Cho","year":"2015","journal-title":"Free Radic Biol Med"},{"key":"2022031300103482300_B46","doi-asserted-by":"crossref","first-page":"E987","DOI":"10.1152\/ajpendo.90234.2008","article-title":"Polymorphisms in metallothionein-1 and -2 genes associated with the risk of type 2 diabetes mellitus and its complications","volume":"294","author":"Yang","year":"2008","journal-title":"Am J Physiol Endocrinol Metab"}],"container-title":["Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/diabetes.diabetesjournals.org\/syndication\/doi\/10.2337\/db15-1274","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.org\/diabetes\/diabetes\/article-pdf\/66\/2\/529\/537518\/db151274.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article-pdf\/66\/2\/529\/537518\/db151274.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T16:31:16Z","timestamp":1667406676000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/diabetes\/article\/66\/2\/529\/35287\/Metallothionein-Is-Downstream-of-Nrf2-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,30]]},"references-count":46,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2016,11,30]]},"published-print":{"date-parts":[[2017,2,1]]}},"URL":"https:\/\/doi.org\/10.2337\/db15-1274","relation":{},"ISSN":["0012-1797","1939-327X"],"issn-type":[{"value":"0012-1797","type":"print"},{"value":"1939-327X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,30]]}}}