{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T08:11:39Z","timestamp":1777623099478,"version":"3.51.4"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T00:00:00Z","timestamp":1700438400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23H02957"],"award-info":[{"award-number":["JP23H02957"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000646","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22H03506"],"award-info":[{"award-number":["JP22H03506"]}],"id":[{"id":"10.13039\/501100000646","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJFS2115"],"award-info":[{"award-number":["JPMJFS2115"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJMS 2021"],"award-info":[{"award-number":["JPMJMS 2021"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2023,12]]},"DOI":"10.1016\/j.ejphar.2023.176190","type":"journal-article","created":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T23:33:15Z","timestamp":1699659195000},"page":"176190","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"special_numbering":"C","title":["Resting phase-administration of lemborexant ameliorates sleep and glucose tolerance in type 2 diabetic mice"],"prefix":"10.1016","volume":"961","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8723-1711","authenticated-orcid":false,"given":"Hiroshi","family":"Tsuneki","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanori","family":"Sugiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyofumi","family":"Sato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8492-6550","authenticated-orcid":false,"given":"Hisakatsu","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanaka","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanta","family":"Kon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Wada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nao","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuya","family":"Okada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Toyooka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Kawasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiro","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Otsubo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4552-783X","authenticated-orcid":false,"given":"Daisuke","family":"Okuzaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruhito","family":"Yasui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyasu","family":"Sasaoka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejphar.2023.176190_bib1","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1124\/jpet.117.241422","article-title":"In vitro and in silico characterization of lemborexant (E2006), a novel dual orexin receptor antagonist","volume":"362","author":"Beuckmann","year":"2017","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejphar.2023.176190_bib2","doi-asserted-by":"crossref","first-page":"zsz076","DOI":"10.1093\/sleep\/zsz076","article-title":"Preclinical in vivo characterization of lemborexant (E2006), a novel dual orexin receptor antagonist for sleep\/wake regulation","volume":"42","author":"Beuckmann","year":"2019","journal-title":"Sleep"},{"key":"10.1016\/j.ejphar.2023.176190_bib3","doi-asserted-by":"crossref","first-page":"E251","DOI":"10.1152\/ajpendo.00401.2007","article-title":"Acutely reduced locomotor activity is a major contributor to Western diet-induced obesity in mice","volume":"294","author":"Bjursell","year":"2008","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"10.1016\/j.ejphar.2023.176190_bib4","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1111\/j.1365-2869.2007.00576.x","article-title":"Daytime sleepiness, exercise, and physical function in older adults","volume":"16","author":"Chasens","year":"2007","journal-title":"J. Sleep Res."},{"key":"10.1016\/j.ejphar.2023.176190_bib5","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/S0140-6736(22)00878-9","article-title":"Comparative effects of pharmacological interventions for the acute and long-term management of insomnia disorder in adults: a systematic review and network meta-analysis","volume":"400","author":"De Crescenzo","year":"2022","journal-title":"Lancet"},{"key":"10.1016\/j.ejphar.2023.176190_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.smrv.2022.101588","article-title":"HPA axis activity in patients with chronic insomnia: a systematic review and meta-analysis of case-control studies","volume":"62","author":"Dressle","year":"2022","journal-title":"Sleep Med. Rev."},{"key":"10.1016\/j.ejphar.2023.176190_bib7","doi-asserted-by":"crossref","first-page":"647","DOI":"10.3390\/nu14030647","article-title":"Glucose uptake by skeletal muscle within the contexts of type 2 diabetes and exercise: an integrated approach","volume":"14","author":"Hulett","year":"2022","journal-title":"Nutrients"},{"key":"10.1016\/j.ejphar.2023.176190_bib8","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1177\/1367493519864756","article-title":"Lower physical activity is associated with daytime sleepiness in children aged 9-12 years","volume":"23","author":"Isa","year":"2019","journal-title":"J. Child Health Care"},{"key":"10.1016\/j.ejphar.2023.176190_bib9","doi-asserted-by":"crossref","DOI":"10.1016\/j.smrv.2021.101456","article-title":"The association of insomnia disorder characterised by objective short sleep duration with hypertension, diabetes and body mass index: a systematic review and meta-analysis","volume":"59","author":"Johnson","year":"2021","journal-title":"Sleep Med. Rev."},{"key":"10.1016\/j.ejphar.2023.176190_bib10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.isci.2019.09.003","article-title":"Differential roles of each orexin receptor signaling in obesity","volume":"20","author":"Kakizaki","year":"2019","journal-title":"iScience"},{"key":"10.1016\/j.ejphar.2023.176190_bib11","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/npr2.12205","article-title":"Evidence-based insomnia treatment strategy using novel orexin antagonists: a review","volume":"41","author":"Kishi","year":"2021","journal-title":"Neuropsychopharmacol. Rep."},{"key":"10.1016\/j.ejphar.2023.176190_bib12","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.cmet.2007.09.006","article-title":"High-fat diet disrupts behavioral and molecular circadian rhythms in mice","volume":"6","author":"Kohsaka","year":"2007","journal-title":"Cell Metab."},{"key":"10.1016\/j.ejphar.2023.176190_bib13","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1530\/JOE-18-0708","article-title":"Chronotherapeutic effect of orexin antagonists on glucose metabolism in diabetic mice","volume":"243","author":"Kon","year":"2019","journal-title":"J. Endocrinol."},{"key":"10.1016\/j.ejphar.2023.176190_bib14","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1515\/bmc-2015-0007","article-title":"Liver X receptors as regulators of metabolism","volume":"6","author":"Korach-Andr\u00e9","year":"2015","journal-title":"Biomol. Concepts"},{"key":"10.1016\/j.ejphar.2023.176190_bib15","doi-asserted-by":"crossref","first-page":"578","DOI":"10.3389\/fendo.2018.00578","article-title":"Involvement of O-GlcNAcylation in the skeletal muscle physiology and physiopathology: focus on muscle metabolism","volume":"9","author":"Lambert","year":"2018","journal-title":"Front. Endocrinol."},{"key":"10.1016\/j.ejphar.2023.176190_bib16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.smrv.2016.02.001","article-title":"The impact of sleep amount and sleep quality on glycemic control in type 2 diabetes: a systematic review and meta-analysis","volume":"31","author":"Lee","year":"2017","journal-title":"Sleep Med. Rev."},{"key":"10.1016\/j.ejphar.2023.176190_bib17","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1038\/nn.3810","article-title":"Motivational activation: a unifying hypothesis of orexin\/hypocretin function","volume":"17","author":"Mahler","year":"2014","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.ejphar.2023.176190_bib18","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1080\/17425255.2020.1817380","article-title":"Clinical pharmacology, efficacy, and safety of orexin receptor antagonists for the treatment of insomnia disorders","volume":"16","author":"Muehlan","year":"2020","journal-title":"Expet Opin. Drug Metab. Toxicol."},{"key":"10.1016\/j.ejphar.2023.176190_bib19","doi-asserted-by":"crossref","first-page":"6371","DOI":"10.1021\/jm400772t","article-title":"Synthesis and evaluation of novel radioligands for positron emission tomography imaging of the orexin-2 receptor","volume":"56","author":"Oi","year":"2013","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejphar.2023.176190_bib20","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/s00125-007-0910-y","article-title":"Exercise: the brittle cornerstone of type 2 diabetes treatment","volume":"51","author":"Praet","year":"2008","journal-title":"Diabetologia"},{"key":"10.1016\/j.ejphar.2023.176190_bib21","doi-asserted-by":"crossref","first-page":"227","DOI":"10.2220\/biomedres.41.227","article-title":"Protective effects of low-intensity exercise on metabolic oxidative capacity and capillarization in skeletal muscle of non-obese diabetic rats","volume":"41","author":"Qatamish","year":"2020","journal-title":"Biomed. Res."},{"key":"10.1016\/j.ejphar.2023.176190_bib22","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1111\/1753-0407.12825","article-title":"SLEep among diabetic patients and their GlycaEmic control (SLEDGE): a pilot observational study","volume":"11","author":"Raj","year":"2019","journal-title":"J. Diabetes"},{"key":"10.1016\/j.ejphar.2023.176190_bib23","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.smrv.2009.04.002","article-title":"The hyperarousal model of insomnia: a review of the concept and its evidence","volume":"14","author":"Riemann","year":"2010","journal-title":"Sleep Med. Rev."},{"key":"10.1016\/j.ejphar.2023.176190_bib24","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/nrn3837","article-title":"The role of orexin in motivated behaviours","volume":"15","author":"Sakurai","year":"2014","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.ejphar.2023.176190_bib25","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1007\/s00125-021-05541-0","article-title":"Sleep disorders in people with type 2 diabetes and associated health outcomes: a review of the literature","volume":"64","author":"Schipper","year":"2021","journal-title":"Diabetologia"},{"key":"10.1016\/j.ejphar.2023.176190_bib26","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1146\/annurev-physiol-060721-095517","article-title":"AMPK and the adaptation to exercise","volume":"84","author":"Spaulding","year":"2022","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.ejphar.2023.176190_bib27","first-page":"37","article-title":"Improvement of glycemic control by treatment for insomnia with suvorexant in type 2 diabetes mellitus","volume":"15","author":"Toi","year":"2018","journal-title":"J. Clin. Transl. Endocrinol."},{"key":"10.1016\/j.ejphar.2023.176190_bib28","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00125-008-0929-8","article-title":"Age-related insulin resistance in hypothalamus and peripheral tissues of orexin knockout mice","volume":"51","author":"Tsuneki","year":"2008","journal-title":"Diabetologia"},{"key":"10.1016\/j.ejphar.2023.176190_bib29","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.npep.2013.02.002","article-title":"Hypothalamic orexin prevents hepatic insulin resistance induced by social defeat stress in mice","volume":"47","author":"Tsuneki","year":"2013","journal-title":"Neuropeptides"},{"key":"10.1016\/j.ejphar.2023.176190_bib30","doi-asserted-by":"crossref","first-page":"459","DOI":"10.2337\/db14-0695","article-title":"Hypothalamic orexin prevents hepatic insulin resistance via daily bidirectional regulation of autonomic nervous system in mice","volume":"64","author":"Tsuneki","year":"2015","journal-title":"Diabetes"},{"key":"10.1016\/j.ejphar.2023.176190_bib31","doi-asserted-by":"crossref","first-page":"4146","DOI":"10.1210\/en.2016-1404","article-title":"Timed inhibition of orexin system by suvorexant improved sleep and glucose metabolism in type 2 diabetic db\/db mice","volume":"157","author":"Tsuneki","year":"2016","journal-title":"Endocrinology"},{"key":"10.1016\/j.ejphar.2023.176190_bib32","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1210\/en.2015-1488","article-title":"Nighttime administration of nicotine improves hepatic glucose metabolism via the hypothalamic orexin system in mice","volume":"157","author":"Tsuneki","year":"2016","journal-title":"Endocrinology"},{"key":"10.1016\/j.ejphar.2023.176190_bib33","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.tem.2016.06.011","article-title":"Sleep control, GPCRs, and glucose metabolism","volume":"27","author":"Tsuneki","year":"2016","journal-title":"Trends Endocrinol. Metab."},{"key":"10.1016\/j.ejphar.2023.176190_bib34","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.diabres.2017.03.032","article-title":"Different impacts of acylated and non-acylated long-acting insulin analogs on neural functions in vitro and in vivo","volume":"129","author":"Tsuneki","year":"2017","journal-title":"Diabetes Res. Clin. Pract."},{"key":"10.1016\/j.ejphar.2023.176190_bib35","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.pharmthera.2017.12.010","article-title":"Chronopathophysiological implications of orexin in sleep disturbances and lifestyle-related disorders","volume":"186","author":"Tsuneki","year":"2018","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.ejphar.2023.176190_bib36","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.111497","article-title":"Hypothalamic orexin prevents non-alcoholic steatohepatitis and hepatocellular carcinoma in obesity","volume":"41","author":"Tsuneki","year":"2022","journal-title":"Cell Rep."},{"key":"10.1016\/j.ejphar.2023.176190_bib37","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/jcb.30179","article-title":"Genes controlling skeletal muscle glucose uptake and their regulation by endurance and resistance exercise","volume":"123","author":"Verbrugge","year":"2022","journal-title":"J. Cell. Biochem."},{"key":"10.1016\/j.ejphar.2023.176190_bib38","doi-asserted-by":"crossref","DOI":"10.1016\/j.smrv.2021.101573","article-title":"The efficacy and safety of dual orexin receptor antagonists in primary insomnia: a systematic review and network meta-analysis","volume":"61","author":"Xue","year":"2022","journal-title":"Sleep Med. Rev."},{"key":"10.1016\/j.ejphar.2023.176190_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.diabres.2020.108412","article-title":"Chronotherapeutic efficacy of suvorexant on sleep quality and metabolic parameters in patients with type 2 diabetes and insomnia","volume":"169","author":"Yoshikawa","year":"2020","journal-title":"Diabetes Res. Clin. Pract."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299923007045?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299923007045?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:15:46Z","timestamp":1777382146000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299923007045"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":39,"alternative-id":["S0014299923007045"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2023.176190","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Resting phase-administration of lemborexant ameliorates sleep and glucose tolerance in type 2 diabetic mice","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2023.176190","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"176190"}}