title: Short-term sleep deprivation with nocturnal light exposure alters time-dependent glucagon-like peptide-1 and insulin secretion in male volunteers.
abstract: The intestinal L cell is the principal source of glucagon-like peptide-1 (GLP-1), a major determinant of insulin release. Because GLP-1 secretion is regulated in a circadian manner in rodents, we investigated whether the activity of the human L cell is also time sensitive. Rhythmic fluctuations in the mRNA levels of canonical clock genes were found in the human NCI-H716 L cell model, which also showed a time-dependent pattern in their response to well-established secretagogues. A diurnal variation in GLP-1 responses to identical meals (850 kcal), served 12 h apart in the normal dark (2300) and light (1100) periods, was also observed in male volunteers maintained under standard sleep and light conditions. These findings suggest the existence of a daily pattern of activity in the human L cell. Moreover, we separately tested the short-term effects of sleep deprivation and nocturnal light exposure on basal and postprandial GLP-1, insulin, and glucose levels in the same volunteers. Sleep deprivation with nocturnal light exposure disrupted the melatonin and cortisol profiles and increased insulin resistance. Moreover, it also induced profound derangements in GLP-1 and insulin responses such that postprandial GLP-1 and insulin levels were markedly elevated and the normal variation in GLP-1 responses was abrogated. These alterations were not observed in sleep-deprived participants maintained under dark conditions, indicating a direct effect of light on the mechanisms that regulate glucose homeostasis. Accordingly, the metabolic abnormalities known to occur in shift workers may be related to the effects of irregular light-dark cycles on these glucoregulatory pathways.
authors.affiliation: Department of Physiology.
authors.forename: Manuel
authors.initials: M
authors.lastname: Gil-Lozano
authors.affiliation: Department of Physiology.
authors.forename: Paola M
authors.initials: PM
authors.lastname: Hunter
authors.affiliation: Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Lucy-Ann
authors.initials: LA
authors.lastname: Behan
authors.affiliation: Institute of Medical Science, and Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Bojana
authors.initials: B
authors.lastname: Gladanac
authors.affiliation: Department of Physiology, Department of Obstetrics and Gynecology, Institute of Medical Science, and Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Casper
authors.affiliation: Department of Physiology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; and p.brubaker@utoronto.ca.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Brubaker
mesh_terms: D000293:Adolescent; D000328:Adult; D056926:CLOCK Proteins / Q000235:genetics; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000378:metabolism* / Q000528:radiation effects; D064368:Healthy Volunteers; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000528:radiation effects; D008027:Light; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000528:radiation effects; D012892:Sleep Deprivation / Q000378:metabolism*; D013997:Time Factors; D055815:Young Adult
chemical_list: D007328:Insulin; D052216:Glucagon-Like Peptide 1; D056926:CLOCK Proteins
keywords: circadian rhythms; clock genes; incretin; light; metabolism; sleep