{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:35:18Z","timestamp":1787499318114,"version":"build-2736575974"},"reference-count":0,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,10]]},"abstract":"\n Disrupted sleep is associated with increased risk of type 2 diabetes. Central actions of orexin, mediated by orexin-1 and orexin-2 receptors, play a crucial role in the maintenance of wakefulness; accordingly, excessive activation of the orexin system causes insomnia. Resting-phase administration of dual orexin receptor antagonist (DORA) has been shown to improve sleep abnormalities and glucose intolerance in type 2 diabetic\n db\/db<\/jats:italic>\n mice, although the mechanism remains unknown. In the present study, to investigate the presence of functional link between sleep and glucose metabolism, the influences of orexin antagonists with or without sleep-promoting effects were compared on glucose metabolism in diabetic mice. In\n db\/db<\/jats:italic>\n mice, 2-SORA-MK1064 (an orexin-2 receptor antagonist) and DORA-12 (a DORA) acutely improved non-rapid eye movement sleep, whereas 1-SORA-1 (an orexin-1 receptor antagonist) had no effect. Chronic resting-phase administration of these drugs improved glucose intolerance, without affecting body weight, food intake, locomotor activity and energy expenditure calculated from O\n 2<\/jats:sub>\n consumption and CO\n 2<\/jats:sub>\n production. The expression levels of proinflammatory factors in the liver were reduced by 2-SORA-MK1064 and DORA-12, but not 1-SORA-1, whereas those in the white adipose tissue were reduced by 1-SORA-1 and DORA-12 more efficiently than 2-SORA-MK1064. When administered chronically at awake phase, these drugs caused no effect. In streptozotocin-induced type 1-like diabetic mice, neither abnormality in sleep\u2013wake behavior nor improvement of glucose intolerance by these drugs were observed. These results suggest that both 1-SORA-type (sleep-independent) and 2-SORA-type (possibly sleep-dependent) mechanisms can provide chronotherapeutic effects against type 2 diabetes associated with sleep disturbances in\n db\/db<\/jats:italic>\n mice.\n <\/jats:p>","DOI":"10.1530\/joe-18-0708","type":"journal-article","created":{"date-parts":[[2019,8,7]],"date-time":"2019-08-07T08:29:40Z","timestamp":1565166580000},"page":"59-72","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":8,"title":["Chronotherapeutic effect of orexin antagonists on glucose metabolism in diabetic mice"],"prefix":"10.1530","volume":"243","author":[{"given":"Kanta","family":"Kon","sequence":"first","affiliation":[{"name":"1Department of Clinical Pharmacology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tsuneki","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisakatsu","family":"Ito","sequence":"additional","affiliation":[{"name":"2Department of Anesthesiology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinori","family":"Takemura","sequence":"additional","affiliation":[{"name":"2Department of Anesthesiology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyofumi","family":"Sato","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuaki","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"2Department of Anesthesiology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Ishii","sequence":"additional","affiliation":[{"name":"3Department of Pathology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakiyo","family":"Sasahara","sequence":"additional","affiliation":[{"name":"3Department of Pathology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assaf","family":"Rudich","sequence":"additional","affiliation":[{"name":"4Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Maeda","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsutomu","family":"Wada","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyasu","family":"Sasaoka","sequence":"additional","affiliation":[{"name":"1Department of Clinical Pharmacology, University of Toyama, Sugitani, Toyama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/243\/1\/JOE-18-0708.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/243\/1\/JOE-18-0708.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:56:41Z","timestamp":1784555801000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/243\/1\/59-72\/5172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/joe-18-0708","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10]]}}}