title: Regulation of Sleep by Insulin-like Peptide System in Drosophila melanogaster.
abstract: OBJECTIVE
  Most organisms have behavioral and physiological circadian rhythms, which are controlled by an endogenous clock. Although genetic analysis has revealed the intracellular mechanism of the circadian clock, the manner in which this clock communicates its temporal information to produce systemic regulation is still largely unknown.
  
  
  METHODS
  Sleep behavior was measured using the Drosophila Activity Monitoring System (DAMS) monitor under a 12 h light:12 h dark cycle and constant darkness (DD), and 5 min without recorded activity were defined as a bout of sleep.
  
  
  RESULTS
  Here we show that Drosophila insulin-like peptides (DILPs) and their receptor (DInR) regulate sleep behavior. All mutants of the seven dilps and the mutant of their receptor exhibit decreases of total sleep except dilp4 mutants, whereas upregulation of DILP and DInR in the nervous system led to increased sleep. Histological analysis identified four previously unidentified neurons expressing DILP: D1, P1, L1, and L2, of which L1 and L2 belong to the LNd and LNv clock neurons that separately regulate different times of sleep. In addition, dilp2 levels significantly decrease when flies were fasted, which is consistent with a previous report that starvation inhibits sleep, further indicating that the dilp system is involved in sleep regulation.
  
  
  CONCLUSIONS
  Taken together, the results indicate that the Drosophila insulin-like peptide system is a crucial regulator of sleep.
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing, Peoples Republic of China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Cong
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing, Peoples Republic of China.
authors.forename: Haili
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing, Peoples Republic of China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing, Peoples Republic of China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing, Peoples Republic of China.
authors.forename: Chunju
authors.initials: C
authors.lastname: An
authors.affiliation: Department of Entomology, College of Agronomy and Biotechnology, China Agricultural University, Beijing, Peoples Republic of China.
authors.forename: Zhangwu
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology / Q000528:radiation effects; D003624:Darkness; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000502:physiology* / Q000528:radiation effects; D005215:Fasting / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008027:Light; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000528:radiation effects; D009479:Neuropeptides; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012890:Sleep / Q000502:physiology* / Q000528:radiation effects
chemical_list: D029721:Drosophila Proteins; C544178:ILP2 protein, Drosophila; D007328:Insulin; D009479:Neuropeptides; C094982:InR protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases
keywords: Drosophila melanogaster; insulin receptor; insulin-like peptide; sleep