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Light at night acutely suppresses melatonin secretion and phase shifts its endogenous circadian rhythm. In contrast, exposure to darkness during the circadian day has not generally been reported to increase circulating melatonin concentrations acutely. Here, in a highly\u2010controlled simulated night shift protocol with 12\u2010h inverted behavioral\/environmental cycles, we unexpectedly found that circulating melatonin levels were significantly increased during daytime sleep (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.0001). This resulted in a secondary melatonin peak during the circadian day in addition to the primary peak during the circadian night, when sleep occurred during the circadian day following an overnight shift. This distinctive diurnal melatonin rhythm with antiphasic peaks could not be readily anticipated from the behavioral\/environmental factors in the protocol (e.g., light exposure, posture, diet, activity) or from current mathematical model simulations of circadian pacemaker output. The observation, therefore, challenges our current understanding of underlying physiological mechanisms that regulate melatonin secretion. Interestingly, the increase in melatonin concentration observed during daytime sleep was positively correlated with the change in timing of melatonin nighttime peak (<jats:italic>p<\/jats:italic>\u2009=\u2009.002), but not with the degree of light\u2010induced melatonin suppression during nighttime wakefulness (<jats:italic>p<\/jats:italic>\u2009=\u2009.92). Both the increase in daytime melatonin concentrations and the change in the timing of the nighttime peak became larger after repeated exposure to simulated night shifts (<jats:italic>p<\/jats:italic>\u2009=\u2009.002 and <jats:italic>p<\/jats:italic>\u2009=\u2009.006, respectively). Furthermore, we found that melatonin secretion during daytime sleep was positively associated with an increase in 24\u2010h glucose and insulin levels during the night shift protocol (<jats:italic>p<\/jats:italic>\u2009=\u2009.014 and <jats:italic>p<\/jats:italic>\u2009=\u2009.027, respectively). Future studies are needed to elucidate the key factor(s) driving the unexpected daytime melatonin secretion and the melatonin rhythm with antiphasic peaks during shifted sleep\/wake schedules, the underlying mechanisms of their relationship with glucose metabolism, and the relevance for diabetes risk among shift workers.<\/jats:p>","DOI":"10.1111\/jpi.12791","type":"journal-article","created":{"date-parts":[[2022,2,8]],"date-time":"2022-02-08T13:39:29Z","timestamp":1644327569000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Unanticipated daytime melatonin secretion on a simulated night shift schedule generates a distinctive 24\u2010h melatonin rhythm with antiphasic daytime and nighttime peaks"],"prefix":"10.1111","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8793-9330","authenticated-orcid":false,"given":"Jingyi","family":"Qian","sequence":"first","affiliation":[{"name":"Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology Brigham and Women's Hospital Boston Massachusetts USA"},{"name":"Division of Sleep Medicine Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Morris","sequence":"additional","affiliation":[{"name":"Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology Brigham and Women's Hospital Boston Massachusetts USA"},{"name":"Division of Sleep Medicine Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1156-7056","authenticated-orcid":false,"given":"Andrew J. K.","family":"Phillips","sequence":"additional","affiliation":[{"name":"School of Psychological Sciences, Turner Institute for Brain and Mental Health Monash University Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4684-4909","authenticated-orcid":false,"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Sleep Medicine Harvard Medical School Boston Massachusetts USA"},{"name":"Medical Biodynamics Program, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadab A.","family":"Rahman","sequence":"additional","affiliation":[{"name":"Division of Sleep Medicine Harvard Medical School Boston Massachusetts USA"},{"name":"Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Sleep Medicine Harvard Medical School Boston Massachusetts USA"},{"name":"Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0350-3132","authenticated-orcid":false,"given":"Kun","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Sleep Medicine Harvard Medical School Boston Massachusetts USA"},{"name":"Medical Biodynamics Program, Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3551-4506","authenticated-orcid":false,"given":"Josephine","family":"Arendt","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medical Sciences University of Surrey Guildford Surrey UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Czeisler","sequence":"additional","affiliation":[{"name":"Division of Sleep Medicine Harvard Medical School Boston Massachusetts USA"},{"name":"Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2014-7582","authenticated-orcid":false,"given":"Frank A. 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