{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T21:35:35Z","timestamp":1783632935794,"version":"3.55.0"},"reference-count":19,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,3,18]]},"abstract":"<jats:p>\n                    The mammalian securin, pituitary tumor transforming gene (PTTG), regulates sister chromatid separation during mitosis. Mice or cell lines deficient in PTTG expression, however, are surprisingly viable. Here we show that PTTG disruption in mice (PTTG\u2212\/\u2212) severely impairs glucose homeostasis leading to diabetes during late adulthood, especially in males associated with nonautoimmune insulinopenia and reversed alpha\/beta cell ratio. Islet beta cell mass in PTTG\u2212\/\u2212 mice was already diminished before development of frank diabetes and only increased minimally during growth. BrdUrd incorporation of islet cells in PTTG-null mice was \u224865% lower (\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.005) than in the WT pancreas, whereas apoptosis rates were similar. PTTG\u2212\/\u2212 beta cells had pleiotropic nuclei, suggesting defects in cell division. The results indicated that securin is indispensable for normal pancreatic beta cell proliferation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0638052100","type":"journal-article","created":{"date-parts":[[2003,3,18]],"date-time":"2003-03-18T18:15:05Z","timestamp":1048011305000},"page":"3428-3432","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":70,"title":["Pituitary tumor transforming gene-null male mice exhibit impaired pancreatic beta cell proliferation and diabetes"],"prefix":"10.1073","volume":"100","author":[{"given":"Zhiyong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Research Institute, University of California School of Medicine, Los Angeles, CA 90048; and Department of Pathology, St. Michael's Hospital, Toronto, ON, Canada M5B1W8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Moro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Research Institute, University of California School of Medicine, Los Angeles, CA 90048; and Department of Pathology, St. Michael's Hospital, Toronto, ON, Canada M5B1W8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalman","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Research Institute, University of California School of Medicine, Los Angeles, CA 90048; and Department of Pathology, St. Michael's Hospital, Toronto, ON, Canada M5B1W8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Run","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Research Institute, University of California School of Medicine, Los Angeles, CA 90048; and Department of Pathology, St. Michael's Hospital, Toronto, ON, Canada M5B1W8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shlomo","family":"Melmed","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cedars-Sinai Research Institute, University of California School of Medicine, Los Angeles, CA 90048; and Department of Pathology, St. Michael's Hospital, Toronto, ON, Canada M5B1W8"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2003,3,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.11.4.9911"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5426.418"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5470.1379"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00340-3"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.15.11.0729"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7123245"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(83)98149-1"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00603-1"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81896-6"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/35050135"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/35048589"},{"key":"e_1_3_3_12_2","first-page":"984","volume":"86","author":"Garcia-Ocana A","year":"2001","unstructured":"A Garcia-Ocana, R C Vasavada, K K Takane, A Cebrian, J C Lopez-Talavera, A F Stewart J Clin Endocrinol Metab 86, 984\u2013988 (2001).","journal-title":"J Clin Endocrinol Metab"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.2.5432"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/15275"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.138.4.5069"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.44.12.1447"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2001.6569"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7917"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200112029"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0638052100","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:24:24Z","timestamp":1649777064000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0638052100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,3,7]]},"references-count":19,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2003,3,18]]}},"alternative-id":["10.1073\/pnas.0638052100"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0638052100","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,3,7]]},"assertion":[{"value":"2002-06-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-12-31","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-03-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}