{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:17:56Z","timestamp":1783549076416,"version":"3.55.0"},"reference-count":61,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2016,4,15]]},"abstract":"<jats:p> Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion, pancreatic \u03b2-cell proliferation, and adiponectin expression in adipocytes. Previously, we showed that long-term intermittent or daily oral administration of GluOC reduced the fasting blood glucose level, improved glucose tolerance, and increased the fasting serum insulin concentration as well as pancreatic \u03b2-cell area in female mice fed a normal or high-fat, high-sucrose diet. We have now performed similar experiments with male mice and found that such GluOC administration induced glucose intolerance, insulin resistance, and adipocyte hypertrophy in those fed a high-fat, high-sucrose diet. In addition, GluOC increased the circulating concentration of testosterone and reduced that of adiponectin in such mice. These phenotypes were not observed in male mice fed a high-fat, high-sucrose diet after orchidectomy, but they were apparent in orchidectomized male mice or intact female mice that were fed such a diet and subjected to continuous testosterone supplementation. Our results thus reveal a sex difference in the effects of GluOC on glucose homeostasis. Given that oral administration of GluOC has been considered a potentially safe and convenient option for the treatment or prevention of metabolic disorders, this sex difference will need to be taken into account in further investigations. <\/jats:p>","DOI":"10.1152\/ajpendo.00334.2015","type":"journal-article","created":{"date-parts":[[2016,2,17]],"date-time":"2016-02-17T04:28:41Z","timestamp":1455683321000},"page":"E662-E675","source":"Crossref","is-referenced-by-count":30,"title":["Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet"],"prefix":"10.1152","volume":"310","author":[{"given":"Yu","family":"Yasutake","sequence":"first","affiliation":[{"name":"Laboratory of Molecular and Cellular Biochemistry,"},{"name":"Division of Orthodontics, Faculty of Dental Science, Kyushu University, Fukuoka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Mizokami","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biochemistry,"},{"name":"OBT Research Center, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyo","family":"Kawakubo-Yasukochi","sequence":"additional","affiliation":[{"name":"Department of Immunological and Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakura","family":"Chishaki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biochemistry,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ichiro","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Orthodontics, Faculty of Dental Science, Kyushu University, Fukuoka, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Division of Applied Pharmacology, Kyushu Dental University, Kitakyushu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Hirata","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Biochemistry,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031777"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2012.201"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422422"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2013.07.018"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1074-z"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.2.268"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.suppl_2.S108"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-003-0450-y"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.4.1000"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711119105"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2014.05.022"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201409111"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2011.04.017"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.06.003"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2007.10.005"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M300239-JLR200"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.06.002"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.23.2.0460"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1368709"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-031458"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215593"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2012.06.002"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-012-2017-7"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2010.12.020"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-1455"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-013-0490-5"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200251200"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2013.08.004"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2004.02007.x"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.05.047"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s002239900432"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2003"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057375"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.09.006"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.9.2734"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2012.04391.x"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.12.018"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1172\/JCI65952"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.08.042"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.004"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311113200"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505186200"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.158063"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.390"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.890130"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-0587"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0263"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.2337\/db14-0272"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2013.37.5.326"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2012.11.029"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/136.3.582"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402367200"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.02.123"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300365200"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72323"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414231200"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/nature01705"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/nm788"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1038\/90984"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047315"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.2217\/clp.13.67"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00334.2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T20:47:12Z","timestamp":1567975632000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00334.2015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4,15]]},"references-count":61,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,4,15]]}},"alternative-id":["10.1152\/ajpendo.00334.2015"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00334.2015","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4,15]]}}}