{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:22:53Z","timestamp":1791246173243,"version":"4.1.0"},"reference-count":45,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2021,8,27]],"date-time":"2021-08-27T00:00:00Z","timestamp":1630022400000},"content-version":"vor","delay-in-days":2752,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,3,1]]},"abstract":"<jats:p>Wolfram syndrome is an autosomal recessive disorder caused by mutations in WFS1 and is characterized by insulin-dependent diabetes mellitus, optic atrophy, and deafness. To investigate the cause of \u03b2-cell failure, we used induced pluripotent stem cells to create insulin-producing cells from individuals with Wolfram syndrome. WFS1-deficient \u03b2-cells showed increased levels of endoplasmic reticulum (ER) stress molecules and decreased insulin content. Upon exposure to experimental ER stress, Wolfram \u03b2-cells showed impaired insulin processing and failed to increase insulin secretion in response to glucose and other secretagogues. Importantly, 4-phenyl butyric acid, a chemical protein folding and trafficking chaperone, restored normal insulin synthesis and the ability to upregulate insulin secretion. These studies show that ER stress plays a central role in \u03b2-cell failure in Wolfram syndrome and indicate that chemical chaperones might have therapeutic relevance under conditions of ER stress in Wolfram syndrome and other forms of diabetes.<\/jats:p>","DOI":"10.2337\/db13-0717","type":"journal-article","created":{"date-parts":[[2013,11,13]],"date-time":"2013-11-13T23:30:54Z","timestamp":1384385454000},"page":"923-933","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":169,"title":["\u03b2-Cell Dysfunction Due to Increased ER Stress in a Stem Cell Model of Wolfram Syndrome"],"prefix":"10.2337","volume":"63","author":[{"given":"Linshan","family":"Shang","sequence":"first","affiliation":[{"name":"The New York Stem Cell Foundation Research Institute, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiqing","family":"Hua","sequence":"additional","affiliation":[{"name":"The New York Stem Cell 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