title: Feeding cycle-dependent circulating insulin fluctuation is not a dominant Zeitgeber for mouse peripheral clocks except in the liver: Differences between endogenous and exogenous insulin effects.
abstract: The master clock in the suprachiasmatic nucleus synchronizes peripheral clocks via humoral and neural signals in mammals. Insulin is thought to be a critical Zeitgeber (synchronizer) for peripheral clocks because it induces transient clock gene expression in cultured cells. However, the extent to which fluctuations in feeding-dependent endogenous insulin affect the temporal expression of clock genes remains unclear. We therefore investigated the temporal expression profiles of clock genes in the peripheral tissues of mice fed for 8 h during either the daytime (DF) or the nighttime (NF) for one week to determine the involvement of feeding cycle-dependent endogenous insulin rhythms in the circadian regulation of peripheral clocks. The phase of circulating insulin fluctuations was reversed in DF compared with NF mice, although those of circulating corticosterone fluctuations and nocturnal locomotor activity were identical between these mice. The reversed feeding cycle affected the circadian phases of Per1 and Per2 gene expression in the liver and not in heart, lung, white adipose and skeletal muscle tissues. On the other hand, injected exogenous insulin significantly induced Akt phosphorylation in the heart and skeletal muscle as well as the liver, and significantly induced Per1 and Per2 gene expression in all examined tissues. These findings suggest that feeding cycles and feeding cycle-dependent endogenous insulin fluctuations are not dominant entrainment signals for peripheral clocks other than the liver, although exogenous insulin might reset peripheral oscillators in mammals.
authors.affiliation: Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan; Department of Applied Biological Science, Graduate School of Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan; Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, Chiba 277-0882, Japan. Electronic address: k-ooishi@aist.go.jp.
authors.forename: Katsutaka
authors.initials: K
authors.lastname: Oishi
authors.affiliation: Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan; Department of Applied Biological Science, Graduate School of Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yasumoto
authors.affiliation: Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Sayaka
authors.initials: S
authors.lastname: Higo-Yamamoto
authors.affiliation: Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: Molecular Physiology and Pathology, School of Pharma-Sciences, Teikyo University, Itabashi, Tokyo 173-8605, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Ohkura
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000235:genetics*; D003345:Corticosterone / Q000097:blood; D004268:DNA-Binding Proteins / Q000235:genetics; D005247:Feeding Behavior / Q000502:physiology*; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D007328:Insulin / Q000097:blood* / Q000494:pharmacology; D008099:Liver / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C498260:Dbp protein, mouse; D007328:Insulin; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D014157:Transcription Factors; D052216:Glucagon-Like Peptide 1; D003345:Corticosterone
keywords: Circadian rhythm; Food entrainable oscillator; GLP-1; Glucocorticoid; Insulin; Mouse; Peripheral clock