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Oral administration of PBA in hIAPP transgenic (hIAPP Tg) mice expressing hIAPP in pancreatic \u03b2 cells counteracted impaired glucose homeostasis and restored glucose\u2010stimulated insulin secretion. Moreover, PBA treatment almost completely prevented the transcriptomic alterations observed in hIAPP Tg islets, including the induction of genes related to inflammation. PBA also increased \u03b2\u2010cell viability and improved insulin secretion in hIAPP Tg islets cultured under glucolipotoxic conditions. Strikingly, PBA not only prevented but even reversed islet amyloid deposition, pointing to a direct effect of PBA on hIAPP. This was supported by\n                    <jats:italic>in silico<\/jats:italic>\n                    calculations uncovering potential binding sites of PBA to monomeric, dimeric, and pentameric fibrillar structures, and by\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays showing inhibition of hIAPP fibril formation by PBA. Collectively, these results uncover a novel beneficial effect of PBA on glucose homeostasis by restoring \u03b2\u2010cell function and preventing amyloid formation in mice expressing hIAPP in \u03b2 cells, highlighting the therapeutic potential of PBA for the treatment of T2D.\u2014Montane, J., de Pablo, S., Casta\u00f1o, C., Rodr\u00edguez\u2010Comas, J., Cadavez, L., Obach, M., Visa, M., Alcarraz\u2010Viz\u00e1n, G., Sanchez\u2010Martinez, M., Nonell\u2010Canals, A., Parrizas, M., Ser\u2010vitja, J.\u2010M., Novials, A. Amyloid\u2010induced \u03b2\u2010cell dysfunction and islet inflammation are ameliorated by 4\u2010phenylbutyrate (PBA) treatment. FASEB J. 31, 5296\u20135306 (2017).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700236r","type":"journal-article","created":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T20:40:36Z","timestamp":1502829636000},"page":"5296-5306","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Amyloid\u2010induced \u03b2\u2010cell dysfunction and islet inflammation are ameliorated by 4\u2010phenylbutyrate (PBA) treatment"],"prefix":"10.1096","volume":"31","author":[{"given":"Joel","family":"Montane","sequence":"first","affiliation":[{"name":"Diabetes and Obesity Research Laboratory Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) Hospital Cl\u00ednic de Barcelona  Barcelona Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de 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