{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T09:28:15Z","timestamp":1790069295325,"version":"4.0.1"},"reference-count":32,"publisher":"Portland Press Ltd.","issue":"9","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,5,1]]},"abstract":"<jats:p>Common polymorphisms within the FTO (fat mass and obesity-associated) gene correlate with increased BMI (body mass index) and a rising risk of Type\u00a02 diabetes. FTO is highly expressed in the brain but has also been detected in peripheral tissues, including the endocrine pancreas, although its function there is unclear. The aim of the present study was to investigate the role of FTO protein in pancreatic \u03b2-cells using a conditional expression system developed in INS-1 cells. INS-1 cells were stably transfected with FTO\u2013HA (haemagluttinin) incorporated under the control of a tetracycline-inducible promoter. Induction of FTO protein resulted in localization of the tagged protein to the nucleus. The level of FTO\u2013HA protein achieved in transfected cells was tightly regulated, and experiments with selective inhibitors revealed that FTO\u2013HA is rapidly degraded via the ubiquitin\/proteasome pathway. The nuclear localization was not altered by proteasome inhibitors, although following treatment with PYR-41, an inhibitor of ubiquitination, some of the protein adopted a perinuclear localization. Unexpectedly, modestly increased expression of FTO\u2013HA selectively enhanced the first phase of insulin secretion when INS-1 monolayers or pseudoislets were stimulated with 20\u00a0mM glucose, whereas the second phase remained unchanged. The mechanism responsible for the potentiation of glucose-induced insulin secretion is unclear; however, further experiments revealed that it did not involve an increase in insulin biosynthesis or any changes in STAT3 (signal transducer and activator of transcription 3) expression. Taken together, these results suggest that the FTO protein may play a hitherto unrecognized role in the control of first-phase insulin secretion in pancreatic \u03b2-cells.<\/jats:p>","DOI":"10.1042\/cs20100416","type":"journal-article","created":{"date-parts":[[2010,11,15]],"date-time":"2010-11-15T11:53:41Z","timestamp":1289822021000},"page":"403-413","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Conditional expression of the <i>FTO<\/i> gene product in rat INS-1 cells reveals its rapid turnover and a role in the profile of glucose-induced insulin secretion"],"prefix":"10.1042","volume":"120","author":[{"given":"Mark\u00a0A.","family":"Russell","sequence":"first","affiliation":[{"name":"Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry (University of Plymouth), Plymouth, Devon PL6 8BU, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel\u00a0G.","family":"Morgan","sequence":"additional","affiliation":[{"name":"Institute of Biomedical and Clinical Science, Peninsula College of Medicine and Dentistry (University of Exeter), Plymouth, Devon PL6 8BU, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2011,1,18]]},"reference":[{"key":"2021113010182117300_B1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1467-789X.2005.00164.x","article-title":"Prevalence of obesity in Great Britain","volume":"6","author":"Rennie","year":"2005","journal-title":"Obes. 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