{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:54:52Z","timestamp":1779170092663,"version":"3.51.4"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Biomed Sci"],"published-print":{"date-parts":[[2014,12]]},"DOI":"10.1186\/1423-0127-21-38","type":"journal-article","created":{"date-parts":[[2014,5,4]],"date-time":"2014-05-04T01:01:55Z","timestamp":1399165315000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Valproate pretreatment protects pancreatic \u03b2-cells from palmitate-induced ER stress and apoptosis by inhibiting glycogen synthase kinase-3\u03b2"],"prefix":"10.1186","volume":"21","author":[{"given":"Shan","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minghui","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abid","family":"Rashid","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Hou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Ning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoping","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2014,5,4]]},"reference":[{"key":"647_CR1","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1146\/annurev-biochem-072909-095555","volume":"81","author":"SH Back","year":"2012","unstructured":"Back SH, Kaufman RJ: Endoplasmic reticulum stress and type 2 diabetes. Annu Rev Biochem. 2012, 81: 767-793.","journal-title":"Annu Rev Biochem"},{"key":"647_CR2","doi-asserted-by":"publisher","first-page":"436","DOI":"10.3945\/ajcn.113.070557","volume":"99","author":"CL Kien","year":"2014","unstructured":"Kien CL, Bunn JY, Stevens R, Bain J, Ikayeva O, Crain K, Koves TR, Muoio DM: Dietary intake of palmitate and oleate has broad impact on systemic and tissue lipid profiles in humans. Am J Clin Nutr. 2014, 99: 436-445.","journal-title":"Am J Clin Nutr"},{"key":"647_CR3","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.plipres.2008.10.002","volume":"48","author":"U Riserus","year":"2009","unstructured":"Riserus U, Willett WC, Hu FB: Dietary fats and prevention of type 2 diabetes. Prog Lipid Res. 2009, 48: 44-51.","journal-title":"Prog Lipid Res"},{"key":"647_CR4","doi-asserted-by":"publisher","first-page":"102","DOI":"10.2337\/diabetes.52.1.102","volume":"52","author":"AE Butler","year":"2003","unstructured":"Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC: Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003, 52: 102-110.","journal-title":"Diabetes"},{"key":"647_CR5","doi-asserted-by":"publisher","first-page":"624","DOI":"10.2337\/diabetes.53.3.624","volume":"53","author":"S Deng","year":"2004","unstructured":"Deng S, Vatamaniuk M, Huang X, Doliba N, Lian MM, Frank A, Velidedeoglu E, Desai NM, Koeberlein B, Wolf B, Barker CF, Naji A, Matschinsky FM, Markmann JF: Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects. Diabetes. 2004, 53: 624-632.","journal-title":"Diabetes"},{"key":"647_CR6","doi-asserted-by":"publisher","first-page":"1013","DOI":"10.1038\/nrd2755","volume":"7","author":"I Kim","year":"2008","unstructured":"Kim I, Xu W, Reed JC: Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov. 2008, 7: 1013-1030.","journal-title":"Nat Rev Drug Discov"},{"key":"647_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4161\/isl.2.1.10456","volume":"2","author":"SG Fonseca","year":"2010","unstructured":"Fonseca SG, Urano F, Burcin M, Gromada J: Stress hypERactivation in the beta-cell. Islets. 2010, 2: 1-9.","journal-title":"Islets"},{"key":"647_CR8","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1177\/153537020322801018","volume":"228","author":"E Araki","year":"2003","unstructured":"Araki E, Oyadomari S, Mori M: Impact of endoplasmic reticulum stress pathway on pancreatic beta-cells and diabetes mellitus. Exp Biol Med (Maywood). 2003, 228: 1213-1217.","journal-title":"Exp Biol Med (Maywood)"},{"key":"647_CR9","doi-asserted-by":"publisher","first-page":"3398","DOI":"10.1210\/en.2005-1494","volume":"147","author":"E Karaskov","year":"2006","unstructured":"Karaskov E, Scott C, Zhang L, Teodoro T, Ravazzola M, Volchuk A: Chronic palmitate but not oleate exposure induces endoplasmic reticulum stress, which may contribute to INS-1 pancreatic beta-cell apoptosis. Endocrinology. 2006, 147: 3398-3407.","journal-title":"Endocrinology"},{"key":"647_CR10","doi-asserted-by":"publisher","first-page":"2600","DOI":"10.1007\/s00125-010-1882-x","volume":"53","author":"Y Liu","year":"2010","unstructured":"Liu Y, Tanabe K, Baronnier D, Patel S, Woodgett J, Cras-Meneur C, Permutt MA: Conditional ablation of Gsk-3beta in islet beta cells results in expanded mass and resistance to fat feeding-induced diabetes in mice. Diabetologia. 2010, 53: 2600-2610.","journal-title":"Diabetologia"},{"key":"647_CR11","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1007\/s00125-007-0914-7","volume":"51","author":"Z Liu","year":"2008","unstructured":"Liu Z, Tanabe K, Bernal-Mizrachi E, Permutt MA: Mice with beta cell overexpression of glycogen synthase kinase-3beta have reduced beta cell mass and proliferation. Diabetologia. 2008, 51: 623-631.","journal-title":"Diabetologia"},{"key":"647_CR12","doi-asserted-by":"publisher","first-page":"44701","DOI":"10.1074\/jbc.M206047200","volume":"277","author":"L Song","year":"2002","unstructured":"Song L, De Sarno P, Jope RS: Central role of glycogen synthase kinase-3beta in endoplasmic reticulum stress-induced caspase-3 activation. J Biol Chem. 2002, 277: 44701-44708.","journal-title":"J Biol Chem"},{"key":"647_CR13","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: Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3. J Cell Sci. 2005, 118: 89-99.","journal-title":"J Cell Sci"},{"key":"647_CR14","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1016\/j.yexcr.2011.02.012","volume":"317","author":"GP Meares","year":"2011","unstructured":"Meares GP, Mines MA, Beurel E, Eom TY, Song L, Zmijewska AA, Jope RS: Glycogen synthase kinase-3 regulates endoplasmic reticulum (ER) stress-induced CHOP expression in neuronal cells. Exp Cell Res. 2011, 317: 1621-1628.","journal-title":"Exp Cell Res"},{"key":"647_CR15","doi-asserted-by":"publisher","first-page":"968","DOI":"10.2337\/diabetes.54.4.968","volume":"54","author":"S Srinivasan","year":"2005","unstructured":"Srinivasan S, Ohsugi M, Liu Z, Fatrai S, Bernal-Mizrachi E, Permutt MA: Endoplasmic reticulum stress-induced apoptosis is partly mediated by reduced insulin signaling through phosphatidylinositol 3-kinase\/Akt and increased glycogen synthase kinase-3beta in mouse insulinoma cells. Diabetes. 2005, 54: 968-975.","journal-title":"Diabetes"},{"key":"647_CR16","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.neuroscience.2014.02.028","volume":"267C","author":"CH Carriere","year":"2014","unstructured":"Carriere CH, Kang NH, Niles LP: Neuroprotection by valproic acid in an intrastriatal rotenone model of Parkinson's disease. Neuroscience. 2014, 267C: 114-121.","journal-title":"Neuroscience"},{"key":"647_CR17","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.neuroscience.2011.01.012","volume":"178","author":"C Penas","year":"2011","unstructured":"Penas C, Verdu E, Asensio-Pinilla E, Guzman-Lenis MS, Herrando-Grabulosa M, Navarro X, Casas C: Valproate reduces CHOP levels and preserves oligodendrocytes and axons after spinal cord injury. Neuroscience. 2011, 178: 33-44.","journal-title":"Neuroscience"},{"key":"647_CR18","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.brainresbull.2011.03.006","volume":"85","author":"JP Hu","year":"2011","unstructured":"Hu JP, Xie JW, Wang CY, Wang T, Wang X, Wang SL, Teng WP, Wang ZY: Valproate reduces tau phosphorylation via cyclin-dependent kinase 5 and glycogen synthase kinase 3 signaling pathways. Brain Res Bull. 2011, 85: 194-200.","journal-title":"Brain Res Bull"},{"key":"647_CR19","doi-asserted-by":"publisher","first-page":"e54792","DOI":"10.1371\/journal.pone.0054792","volume":"8","author":"J Yi","year":"2013","unstructured":"Yi J, Zhang L, Tang B, Han W, Zhou Y, Chen Z, Jia D, Jiang H: Sodium valproate alleviates neurodegeneration in SCA3\/MJD via suppressing apoptosis and rescuing the hypoacetylation levels of histone H3 and H4. PLoS One. 2013, 8: e54792-","journal-title":"PLoS One"},{"key":"647_CR20","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1016\/S0028-3908(02)00215-0","volume":"43","author":"P De Sarno","year":"2002","unstructured":"De Sarno P, Li X, Jope RS: Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithium. Neuropharmacology. 2002, 43: 1158-1164.","journal-title":"Neuropharmacology"},{"key":"647_CR21","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1210\/endo.142.1.7863","volume":"142","author":"SP Cousin","year":"2001","unstructured":"Cousin SP, Hugl SR, Wrede CE, Kajio H, Myers MG, Rhodes CJ: Free fatty acid-induced inhibition of glucose and insulin-like growth factor I-induced deoxyribonucleic acid synthesis in the pancreatic beta-cell line INS-1. Endocrinology. 2001, 142: 229-240.","journal-title":"Endocrinology"},{"key":"647_CR22","doi-asserted-by":"publisher","first-page":"E540","DOI":"10.1152\/ajpendo.00478.2007","volume":"294","author":"E Lai","year":"2008","unstructured":"Lai E, Bikopoulos G, Wheeler MB, Rozakis-Adcock M, Volchuk A: Differential activation of ER stress and apoptosis in response to chronically elevated free fatty acids in pancreatic beta-cells. Am J Physiol Endocrinol Metab. 2008, 294: E540-550.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"647_CR23","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1016\/j.neurobiolaging.2013.11.022","volume":"35","author":"Q Jiang","year":"2014","unstructured":"Jiang Q, Wang L, Guan Y, Xu H, Niu Y, Han L, Wei YP, Lin L, Chu J, Wang Q, Yang Y, Pei L, Wang JZ, Tian Q: Golgin-84-associated Golgi fragmentation triggers tau hyperphosphorylation by activation of cyclin-dependent kinase-5 and extracellular signal-regulated kinase. Neurobiol Aging. 2014, 35: 1352-1363.","journal-title":"Neurobiol Aging"},{"key":"647_CR24","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1038\/pr.2012.123","volume":"72","author":"J Ye","year":"2012","unstructured":"Ye J, Zheng R, Wang Q, Liao L, Ying Y, Lu H, Cianflone K, Ning Q, Luo X: Downregulating SOCS3 with siRNA ameliorates insulin signaling and glucose metabolism in hepatocytes of IUGR rats with catch-up growth. Pediatr Res. 2012, 72: 550-559.","journal-title":"Pediatr Res"},{"key":"647_CR25","doi-asserted-by":"publisher","first-page":"2308","DOI":"10.1242\/jcs.026062","volume":"121","author":"DA Cunha","year":"2008","unstructured":"Cunha DA, Hekerman P, Ladriere L, Bazarra-Castro A, Ortis F, Wakeham MC, Moore F, Rasschaert J, Cardozo AK, Bellomo E, Overbergh L, Mathieu C, Lupi R, Hai T, Herchuelz A, Marchetti P, Rutter GA, Eizirik DL, Cnop M: Initiation and execution of lipotoxic ER stress in pancreatic beta-cells. J Cell Sci. 2008, 121: 2308-2318.","journal-title":"J Cell Sci"},{"key":"647_CR26","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/S0306-4522(02)00655-3","volume":"116","author":"JF Wang","year":"2003","unstructured":"Wang JF, Azzam JE, Young LT: Valproate inhibits oxidative damage to lipid and protein in primary cultured rat cerebrocortical cells. Neuroscience. 2003, 116: 485-489.","journal-title":"Neuroscience"},{"key":"647_CR27","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.molbrainres.2004.10.021","volume":"134","author":"GS Peng","year":"2005","unstructured":"Peng GS, Li G, Tzeng NS, Chen PS, Chuang DM, Hsu YD, Yang S, Hong JS: Valproate pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity in rat primary midbrain cultures: role of microglia. Brain Res Mol Brain Res. 2005, 134: 162-169.","journal-title":"Brain Res Mol Brain Res"},{"key":"647_CR28","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1176\/ajp.153.6.765","volume":"153","author":"CL Bowden","year":"1996","unstructured":"Bowden CL, Janicak PG, Orsulak P, Swann AC, Davis JM, Calabrese JR, Goodnick P, Small JG, Rush AJ, Kimmel SE, Risch SC, Morris DD: Relation of serum valproate concentration to response in mania. Am J Psychiatry. 1996, 153: 765-770.","journal-title":"Am J Psychiatry"},{"key":"647_CR29","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/nrendo.2011.183","volume":"8","author":"L Chen","year":"2012","unstructured":"Chen L, Magliano DJ, Zimmet PZ: The worldwide epidemiology of type 2 diabetes mellitus\u2013present and future perspectives. Nat Rev Endocrinol. 2012, 8: 228-236.","journal-title":"Nat Rev Endocrinol"},{"key":"647_CR30","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1038\/nature05482","volume":"444","author":"SE Kahn","year":"2006","unstructured":"Kahn SE, Hull RL, Utzschneider KM: Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006, 444: 840-846.","journal-title":"Nature"},{"key":"647_CR31","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.bcp.2008.04.010","volume":"76","author":"YY Chen","year":"2008","unstructured":"Chen YY, Chen G, Fan Z, Luo J, Ke ZJ: GSK3beta and endoplasmic reticulum stress mediate rotenone-induced death of SK-N-MC neuroblastoma cells. Biochem Pharmacol. 2008, 76: 128-138.","journal-title":"Biochem Pharmacol"},{"key":"647_CR32","doi-asserted-by":"publisher","first-page":"E576","DOI":"10.1152\/ajpendo.00523.2006","volume":"293","author":"W Guo","year":"2007","unstructured":"Guo W, Wong S, Xie W, Lei T, Luo Z: Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3\u00a0T3-L1 and rat primary preadipocytes. Am J Physiol Endocrinol Metab. 2007, 293: E576-586.","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"647_CR33","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.ejphar.2006.03.076","volume":"539","author":"JS Lai","year":"2006","unstructured":"Lai JS, Zhao C, Warsh JJ, Li PP: Cytoprotection by lithium and valproate varies between cell types and cellular stresses. Eur J Pharmacol. 2006, 539: 18-26.","journal-title":"Eur J Pharmacol"},{"key":"647_CR34","doi-asserted-by":"publisher","first-page":"3989","DOI":"10.1074\/jbc.M607627200","volume":"282","author":"M Cnop","year":"2007","unstructured":"Cnop M, Ladriere L, Hekerman P, Ortis F, Cardozo AK, Dogusan Z, Flamez D, Boyce M, Yuan J, Eizirik DL: Selective inhibition of eukaryotic translation initiation factor 2 alpha dephosphorylation potentiates fatty acid-induced endoplasmic reticulum stress and causes pancreatic beta-cell dysfunction and apoptosis. J Biol Chem. 2007, 282: 3989-3997.","journal-title":"J Biol Chem"},{"key":"647_CR35","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.2337\/db06-1253","volume":"56","author":"P Pirot","year":"2007","unstructured":"Pirot P, Ortis F, Cnop M, Ma Y, Hendershot LM, Eizirik DL, Cardozo AK: Transcriptional regulation of the endoplasmic reticulum stress gene chop in pancreatic insulin-producing cells. Diabetes. 2007, 56: 1069-1077.","journal-title":"Diabetes"},{"key":"647_CR36","doi-asserted-by":"publisher","first-page":"e18146","DOI":"10.1371\/journal.pone.0018146","volume":"6","author":"K Tanabe","year":"2011","unstructured":"Tanabe K, Liu Y, Hasan SD, Martinez SC, Cras-Meneur C, Welling CM, Bernal-Mizrachi E, Tanizawa Y, Rhodes CJ, Zmuda E, Hai T, Abumrad NA, Permutt MA: Glucose and fatty acids synergize to promote B-cell apoptosis through activation of glycogen synthase kinase 3beta independent of JNK activation. PLoS One. 2011, 6: e18146-","journal-title":"PLoS One"},{"key":"647_CR37","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1007\/s00018-007-7045-7","volume":"64","author":"JE Forde","year":"2007","unstructured":"Forde JE, Dale TC: Glycogen synthase kinase 3: a key regulator of cellular fate. Cell Mol Life Sci. 2007, 64: 1930-1944.","journal-title":"Cell Mol Life Sci"},{"key":"647_CR38","doi-asserted-by":"publisher","first-page":"930710","DOI":"10.1155\/2012\/930710","volume":"2012","author":"KM Jacobs","year":"2012","unstructured":"Jacobs KM, Bhave SR, Ferraro DJ, Jaboin JJ, Hallahan DE, Thotala D: GSK-3beta: A Bifunctional Role in Cell Death Pathways. Int J Cell Biol. 2012, 2012: 930710-","journal-title":"Int J Cell Biol"}],"container-title":["Journal of Biomedical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/1423-0127-21-38.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T12:26:55Z","timestamp":1630585615000},"score":1,"resource":{"primary":{"URL":"https:\/\/jbiomedsci.biomedcentral.com\/articles\/10.1186\/1423-0127-21-38"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,4]]},"references-count":38,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,12]]}},"alternative-id":["647"],"URL":"https:\/\/doi.org\/10.1186\/1423-0127-21-38","relation":{},"ISSN":["1423-0127"],"issn-type":[{"value":"1423-0127","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,4]]},"assertion":[{"value":"1 February 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2014","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2014","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"38"}}