{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:44:32Z","timestamp":1791081872509,"version":"4.1.0"},"reference-count":73,"publisher":"Wiley","issue":"s1","license":[{"start":{"date-parts":[[2011,8,8]],"date-time":"2011-08-08T00:00:00Z","timestamp":1312761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p>\n                    The development of the endocrine pancreas and the differentiation of its five cell types,\n                    <jats:italic>\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>\u03b4<\/jats:italic>\n                    ,\n                    <jats:italic>\u03b5<\/jats:italic>\n                    and pancreatic polypeptide (PP) cells, are a highly complex and tightly regulated process. Proper differentiation and function of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010 and\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cells are critical for blood glucose homeostasis. These processes are governed by multiple transcription factors and other signalling systems, and its dysregulation results in diabetes. The differentiation of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010cells and the maintenance of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010cell function can be influenced at several stages during development and in the maturing islet. Many transcription factors, such as neurogenin 3 (Ngn3), pancreatic duodenal homeobox 1 (Pdx1) and regulatory factor x6 (Rfx6), play a crucial role in the determination of the endocrine cell fate, while other transcription factors, such as aristaless\u2010related homeobox (Arx) and forkhead box A2 (Foxa2), are implicated in the initial or terminal differentiation of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010cells.\n                    <jats:italic>In vivo<\/jats:italic>\n                    and\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies have shown that preproglucagon transcription, and therefore the maintenance of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010cell function, is regulated by several factors, including forkhead box A1 (Foxa1), paired box 6 (Pax6), brain4 (Brn4) and islet\u20101 (Isl\u20101). Detailed information about the regulation of normal and abnormal\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010cell differentiation gives insight into the pathogenesis of diabetes, identifies further targets for diabetes treatment and provides clues for the reprogramming of\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010 to\n                    <jats:italic>\u03b2<\/jats:italic>\n                    \u2010cells for replacement therapy.\n                  <\/jats:p>","DOI":"10.1111\/j.1463-1326.2011.01440.x","type":"journal-article","created":{"date-parts":[[2011,8,8]],"date-time":"2011-08-08T11:54:32Z","timestamp":1312804472000},"page":"13-20","source":"Crossref","is-referenced-by-count":48,"title":["Transcriptional regulation of\n                    <i>\u03b1<\/i>\n                    \u2010cell differentiation"],"prefix":"10.1111","volume":"13","author":[{"given":"N. 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