title: Daily Fasting Blood Glucose Rhythm in Male Mice: A Role of the Circadian Clock in the Liver.
abstract: Fasting blood glucose (FBG) and hepatic glucose production are regulated according to a circadian rhythm. An early morning increase in FBG levels, which is pronounced among diabetic patients, is known as the dawn phenomenon. Although the intracellular circadian clock generates various molecular rhythms, whether the hepatic clock is involved in FBG rhythm remains unclear. To address this issue, we investigated the effects of phase shift and disruption of the hepatic clock on the FBG rhythm. In both C57BL/6J and diabetic ob/ob mice, FBG exhibited significant daily rhythms with a peak at the beginning of the dark phase. Light-phase restricted feeding altered the phase of FBG rhythm mildly in C57BL/6J mice and greatly in ob/ob mice, in concert with the phase shifts of mRNA expression rhythms of the clock and glucose production-related genes in the liver. Moreover, the rhythmicity of FBG and Glut2 expression was not detected in liver-specific Bmal1-deficient mice. Furthermore, treatment with octreotide suppressed the plasma growth hormone concentration but did not affect the hepatic mRNA expression of the clock genes or the rise in FBG during the latter half of the resting phase in C57BL/6J mice. These results suggest that the hepatic circadian clock plays a critical role in regulating the daily FBG rhythm, including the dawn phenomenon.
authors.affiliation: Division of Clinical Pharmacology (H.A., K.U., A.F.), Department of Pharmacology, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan; and Department of Health Science (S.S.), School of Pharmacy, Nihon University, Funabashi, Chiba 274-8555, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ando
authors.affiliation: Division of Clinical Pharmacology (H.A., K.U., A.F.), Department of Pharmacology, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan; and Department of Health Science (S.S.), School of Pharmacy, Nihon University, Funabashi, Chiba 274-8555, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Ushijima
authors.affiliation: Division of Clinical Pharmacology (H.A., K.U., A.F.), Department of Pharmacology, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan; and Department of Health Science (S.S.), School of Pharmacy, Nihon University, Funabashi, Chiba 274-8555, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shimba
authors.affiliation: Division of Clinical Pharmacology (H.A., K.U., A.F.), Department of Pharmacology, School of Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan; and Department of Health Science (S.S.), School of Pharmacy, Nihon University, Funabashi, Chiba 274-8555, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology*; D002940:Circadian Rhythm; D005215:Fasting / Q000097:blood*; D005943:Gluconeogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D056950:Period Circadian Proteins; D056926:CLOCK Proteins; C538944:Clock protein, mouse; D010729:Phosphoenolpyruvate Carboxykinase (GTP)