{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:18:08Z","timestamp":1790432288523,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T00:00:00Z","timestamp":1585180800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T00:00:00Z","timestamp":1585180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Endocrinol Invest"],"published-print":{"date-parts":[[2020,9]]},"DOI":"10.1007\/s40618-020-01228-2","type":"journal-article","created":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T13:03:32Z","timestamp":1585227812000},"page":"1317-1325","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Effect of 4-phenylbutyrate and valproate on dominant mutations of WFS1 gene in Wolfram syndrome"],"prefix":"10.1007","volume":"43","author":[{"given":"K.","family":"Batjargal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Tajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. F.","family":"Jimbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Yamagata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,26]]},"reference":[{"key":"1228_CR1","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1093\/hmg\/ddg214","volume":"12","author":"S Hofmann","year":"2003","unstructured":"Hofmann S, Philbrook C, Gerbitz KD, Bauer MF (2003) Wolfram syndrome: structural and functional analyses of mutant and wild-type wolframin, the WFS1 gene product. Hum Mol Genet 12:2003\u20132012. https:\/\/doi.org\/10.1093\/hmg\/ddg214","journal-title":"Hum Mol Genet"},{"key":"1228_CR2","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1111\/pedi.12513","volume":"18","author":"S Morikawa","year":"2017","unstructured":"Morikawa S, Tajima T, Nakamura A, Ishizu K, Ariga T (2017) A novel heterozygous mutation of the WFS1 gene leading to constitutive endoplasmic reticulum stress is the cause of Wolfram syndrome. Pediatr Diabetes 18:934\u2013941. https:\/\/doi.org\/10.1111\/pedi.12513","journal-title":"Pediatr Diabetes"},{"key":"1228_CR3","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1111\/j.1399-0004.2010.01522.x","volume":"79","author":"L Rigoli","year":"2001","unstructured":"Rigoli L, Lombardo F, Di Bella C (2001) Wolfram syndrome and WFS1 gene. Clin Genet 79:103\u2013117. https:\/\/doi.org\/10.1111\/j.1399-0004.2010.01522.x","journal-title":"Clin Genet"},{"key":"1228_CR4","doi-asserted-by":"publisher","first-page":"e106906","DOI":"10.1371\/journal.pone.0106906","volume":"9","author":"K Matsunaga","year":"2014","unstructured":"Matsunaga K, Tanabe K, Inoue H et al (2014) Wolfram syndrome in the Japanese population; molecular analysis of WFS1 gene and characterization of clinical features. PLoS ONE 9:e106906. https:\/\/doi.org\/10.1371\/journal.pone.0106906","journal-title":"PLoS ONE"},{"key":"1228_CR5","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1007\/s11892-015-0702-6","volume":"16","author":"F Urano","year":"2016","unstructured":"Urano F (2016) Wolfram syndrome: diagnosis, management, and treatment. Curr Diab Rep 16:6. https:\/\/doi.org\/10.1007\/s11892-015-0702-6","journal-title":"Curr Diab Rep"},{"key":"1228_CR6","doi-asserted-by":"publisher","first-page":"3943","DOI":"10.2337\/db13-0571","volume":"62","author":"LL Bonnycastle","year":"2013","unstructured":"Bonnycastle LL, Chines PS, Hara T et al (2013) Autosomal dominant diabetes arising from a Wolfram syndrome 1 mutation. Diabetes 62:3943\u20133950. https:\/\/doi.org\/10.2337\/db13-0571","journal-title":"Diabetes"},{"key":"1228_CR7","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.2337\/db16-1296","volume":"66","author":"E De Franco","year":"2017","unstructured":"De Franco E, Flanagan SE, Yagi T et al (2017) Dominant ER Stress-Inducing WFS1 mutations underlie a genetic syndrome of neonatal\/infancy-onset diabetes, congenital sensorineural deafness, and congenital cataracts. Diabetes 66:2044\u20132053. https:\/\/doi.org\/10.2337\/db16-1296","journal-title":"Diabetes"},{"key":"1228_CR8","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1136\/jmg.2005.034892","volume":"43","author":"H Eiberg","year":"2006","unstructured":"Eiberg H, Hansen L, Kjer B et al (2006) Autosomal dominant optic atrophy associated with hearing impairment and impaired glucose regulation caused by a missense mutation in the WFS1 gene. J Med Genet 43:435\u2013440. https:\/\/doi.org\/10.1136\/jmg.2005.034892","journal-title":"J Med Genet"},{"key":"1228_CR9","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1038\/sj.ejhg.5201491","volume":"13","author":"L Hansen","year":"2005","unstructured":"Hansen L, Eiberg H, Barrett T, Bek T, Kj\u00e6rsgaard P, Tranebj\u00e6rg L, Rosenberg T (2005) Mutation analysis of the WFS1 gene in seven danish Wolfram syndrome families; four new mutations identified. Eur J Hum Genet 13:1275\u20131284. https:\/\/doi.org\/10.1038\/sj.ejhg.5201491","journal-title":"Eur J Hum Genet"},{"key":"1228_CR10","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s00418-003-0495-6","volume":"119","author":"K Cryns","year":"2003","unstructured":"Cryns K, Thys S, Van Laer L et al (2003) The WFS1 gene, responsible for low frequency sensorineural hearing loss and Wolfram syndrome, is expressed in a variety of inner ear cells. Histochem Cell Biol 119:247\u2013256","journal-title":"Histochem Cell Biol"},{"key":"1228_CR11","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1007\/s10038-007-0144-3","volume":"52","author":"H Fukuoka","year":"2017","unstructured":"Fukuoka H, Kanda Y, Ohta S, Usami S (2017) Mutations in the WFS1 gene are a frequent cause of autosomal dominant nonsyndromic low-frequency hearing loss in Japanese. J Hum Genet 52:510\u2013515. https:\/\/doi.org\/10.1007\/s10038-007-0144-3","journal-title":"J Hum Genet"},{"key":"1228_CR12","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1186\/s12967-019-1993-1","volume":"17","author":"MT Pallotta","year":"2019","unstructured":"Pallotta MT, Tascini G, Crispoldi R, Orabona C, Mondanelli G, Grohmann U, Esposito S (2019) Wolfram syndrome, a rare neurodegenerative disease: from pathogenesis to future treatment perspectives. J Transl Med 17:238. https:\/\/doi.org\/10.1186\/s12967-019-1993-1","journal-title":"J Transl Med"},{"key":"1228_CR13","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.coph.2009.07.003","volume":"9","author":"SG Fonseca","year":"2009","unstructured":"Fonseca SG, Burcin M, Gromada J, Urano F (2009) Endoplasmic reticulum stress in beta-cells and development of diabetes. Curr Opin Pharmacol 9:763\u2013770. https:\/\/doi.org\/10.1016\/j.coph.2009.07.003","journal-title":"Curr Opin Pharmacol"},{"key":"1228_CR14","doi-asserted-by":"publisher","first-page":"39609","DOI":"10.1074\/jbc.M507426200","volume":"280","author":"SG Fonseca","year":"2005","unstructured":"Fonseca SG, Fukuma M, Lipson KL, Nguyen LX, Allen JR, Oka Y, Urano F (2005) WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic \u03b2-cells. J Biol Chem 280:39609\u201339615. https:\/\/doi.org\/10.1074\/jbc.M507426200","journal-title":"J Biol Chem"},{"key":"1228_CR15","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.biocel.2015.01.015","volume":"61","author":"PS Kolb","year":"2015","unstructured":"Kolb PS, Ayaub EA, Zhou W, Yum V, Dickhout JG, Ask K (2015) The therapeutic effects of 4-phenylbutyric acid in maintaining proteostasis. Int J Bio Cell Biol 61:45\u201352. https:\/\/doi.org\/10.1016\/j.biocel.2015.01.015","journal-title":"Int J Bio Cell Biol"},{"key":"1228_CR16","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1167\/iovs.06-0943","volume":"48","author":"GH Yam","year":"2007","unstructured":"Yam GH, Gaplovska-Kysela K, Zuber C, Roth J (2007) Sodium 4-phenylbutyrate acts as a chemical chaperone on misfolded myocilin to rescue cells from endoplasmic reticulum stress and apoptosis. Invest Opthtalmo Vis Sci 48:1683\u20131690. https:\/\/doi.org\/10.1167\/iovs.06-0943","journal-title":"Invest Opthtalmo Vis Sci"},{"key":"1228_CR17","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1006\/mthe.2002.0639","volume":"6","author":"PL Zeitlin","year":"2002","unstructured":"Zeitlin PL, Diener-West M, Rubenstein RC, Boyle MP, Lee CKK, Brass-Ernst L (2002) Evidence of CFTR function in cystic fibrosis after systemic administration of 4-phenylbutyrate. Mol Ther 6:119\u2013126. https:\/\/doi.org\/10.1006\/mthe.2002.0639","journal-title":"Mol Ther"},{"key":"1228_CR18","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.atherosclerosis.2017.09.034","volume":"266","author":"A Huang","year":"2017","unstructured":"Huang A, Young TL, Dang VT, Shi Y, McAlpine CS, Werstuck GH (2017) 4-phenylbutyrate and valproate treatment attenuates the progression of atherosclerosis and stabilizes existing plaques. Atherosclerosis 266:103\u2013112. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2017.09.034","journal-title":"Atherosclerosis"},{"key":"1228_CR19","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1007\/s12272-012-0718-2","volume":"35","author":"DS Kim","year":"2012","unstructured":"Kim DS, Li B, Rhew KY et al (2012) The regulatory mechanism of 4-phenylbutyric acid against ER stress-induced autophagy in human gingival fibroblasts. Arch Pharmacal Res 35:1269\u20131278. https:\/\/doi.org\/10.1007\/s12272-012-0718-2","journal-title":"Arch Pharmacal Res"},{"key":"1228_CR20","doi-asserted-by":"publisher","first-page":"923","DOI":"10.2337\/db13-0717","volume":"63","author":"L Shang","year":"2014","unstructured":"Shang L, Hua H, Foo K et al (2014) \u03b2-cell dysfunction due to increased ER stress in a stem cell model of Wolfram syndrome. Diabetes 63:923\u2013933. https:\/\/doi.org\/10.2337\/db13-0717","journal-title":"Diabetes"},{"key":"1228_CR21","doi-asserted-by":"publisher","first-page":"e101797","DOI":"10.1371\/journal.pone.0101797","volume":"9","author":"L Cadavez","year":"2014","unstructured":"Cadavez L, Montane J, Alcarraz-Viz\u00e1n G, Visa M, Vidal-F\u00e0brega L, Servitja J-M, Novials A (2014) Chaperones ameliorate beta cell dysfunction associated with human islet amyloid polypeptide overexpression. PLoS ONE 9:e101797. https:\/\/doi.org\/10.1371\/journal.pone.0101797","journal-title":"PLoS ONE"},{"key":"1228_CR22","doi-asserted-by":"publisher","first-page":"e4134","DOI":"10.1371\/journal.pone.0004134","volume":"4","author":"C Kakiuchi","year":"2009","unstructured":"Kakiuchi C, Ishigaki S, Oslowski CM, Fonseca SG, Kato T, Urano F (2009) Valproate, a mood stabilizer, induces WFS1 expression and modulates its interaction with ER stress protein GRP94. PLoS ONE 4:e4134. https:\/\/doi.org\/10.1371\/journal.pone.0004134","journal-title":"PLoS ONE"},{"key":"1228_CR23","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1242\/jcs.01562","volume":"118","author":"AJ Kim","year":"2005","unstructured":"Kim AJ, Shi Y, Austin RC, Werstuck GH (2005) Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3. J Cell Sci 118:89\u201399. https:\/\/doi.org\/10.1242\/jcs.01562","journal-title":"J Cell Sci"},{"key":"1228_CR24","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3390\/ijms18020315","volume":"18","author":"Z Li","year":"2017","unstructured":"Li Z, Wu F, Zhang X (2017) Valproate attenuates endoplasmic reticulum stress-induced apoptosis in SH-SY5Y cells via the AKT\/GSK3\u03b2 signaling pathway. Int J Mol Sci 18:315. https:\/\/doi.org\/10.3390\/ijms18020315","journal-title":"Int J Mol Sci"},{"key":"1228_CR25","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/1423-0127-21-38","volume":"21","author":"S Huang","year":"2014","unstructured":"Huang S, Zhu M, Wu W et al (2014) Valproate pretreatment protects pancreatic \u03b2-cells from palmitate-induced ER stress and apoptosis by inhibiting glycogen synthase kinase-3\u03b2. J Biomed Sci 21:38. https:\/\/doi.org\/10.1186\/1423-0127-21-38","journal-title":"J Biomed Sci"},{"key":"1228_CR26","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s13105-011-0088-0","volume":"67","author":"A Terasmaa","year":"2011","unstructured":"Terasmaa A, Soomets U, Oflijan J (2011) Wfs1 mutation makes mice sensitive to insulin-like effect of acute valproic acid and resistant to streptozocin. J Physiol Biochem 67:381\u2013390. https:\/\/doi.org\/10.1007\/s13105-011-0088-0","journal-title":"J Physiol Biochem"},{"key":"1228_CR27","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1172\/JCI39678","volume":"120","author":"SG Fonseca","year":"2010","unstructured":"Fonseca SG, Ishigaki S, Oslowski CM et al (2010) Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells. J Clin Inverst 120:744\u2013755. https:\/\/doi.org\/10.1172\/JCI39678","journal-title":"J Clin Inverst"},{"key":"1228_CR28","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.devcel.2007.07.005","volume":"13","author":"J Wu","year":"2007","unstructured":"Wu J, Rutkowski DT, Dubois M et al (2007) ATF6\u03b1 optimizes long-term endoplasmic reticulum function to protect cells from chronic stress. Dev Cell 13:351\u2013364. https:\/\/doi.org\/10.1016\/j.devcel.2007.07.005","journal-title":"Dev Cell"},{"key":"1228_CR29","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1093\/jb\/mvr143","volume":"151","author":"H Nishitoh","year":"2011","unstructured":"Nishitoh H (2011) CHOP is a multifunctional transcription factor in the ER stress response. J Biochem 151:217\u2013219. https:\/\/doi.org\/10.1093\/jb\/mvr143","journal-title":"J Biochem"},{"key":"1228_CR30","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1530\/eje.1.01945","volume":"153","author":"K Ueda","year":"2005","unstructured":"Ueda K, Kawano J, Takeda K et al (2005) Endoplasmic reticulum stress induces Wfs1 gene expression in pancreatic \u03b2-cells via transcriptional activation. Eur J Endocrinol 153:167\u2013176. https:\/\/doi.org\/10.1530\/eje.1.01945","journal-title":"Eur J Endocrinol"},{"key":"1228_CR31","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1093\/hmg\/ddl081","volume":"15","author":"T Yamada","year":"2006","unstructured":"Yamada T, Ishihara H, Tamura A et al (2006) WFS1-deficiency increases endoplasmic reticulum stress, impairs cell cycle progression and triggers the apoptotic pathway specifically in pancreatic \u03b2-cells. Hum Mol Genet 15:1600\u20131609. https:\/\/doi.org\/10.1093\/hmg\/ddl081","journal-title":"Hum Mol Genet"},{"key":"1228_CR32","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1210\/en.2013-1519","volume":"155","author":"T Hara","year":"2014","unstructured":"Hara T, Mahadevan J, Kanekura K et al (2014) Calcium efflux from the endoplasmic reticulum leads to \u03b2-cell death. Endocrinology 155:758\u2013768. https:\/\/doi.org\/10.1210\/en.2013-1519","journal-title":"Endocrinology"}],"container-title":["Journal of Endocrinological Investigation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-020-01228-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s40618-020-01228-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s40618-020-01228-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T00:22:08Z","timestamp":1616718128000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s40618-020-01228-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,26]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["1228"],"URL":"https:\/\/doi.org\/10.1007\/s40618-020-01228-2","relation":{},"ISSN":["1720-8386"],"issn-type":[{"value":"1720-8386","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,26]]},"assertion":[{"value":"25 November 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"On behalf of all authors, the corresponding author states that there is no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This article does not contain any studies involving human participants performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Research involving human participants and\/or animals"}},{"value":"For this type of study, formal consent is not required.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}