title: The suprachiasmatic nucleus controls the daily variation of plasma glucose via the autonomic output to the liver: are the clock genes involved?
abstract: In order to drive tissue-specific rhythmic outputs, the master clock, located in the suprachiasmatic nucleus (SCN), is thought to reset peripheral oscillators via either chemical and hormonal cues or neural connections. Recently, the daily rhythm of plasma glucose (characterized by a peak before the onset of the activity period) has been shown to be directly driven by the SCN, independently of the SCN control of rhythmic feeding behaviour. Indeed, the daily variation in glucose was not impaired unless the scheduled feeding regimen (six-meal schedule) was associated with an SCN lesion. Here we show that the rhythmicity of both clock-gene mRNA expression in the liver and plasma glucose is not abolished under such a regular feeding schedule. Because the onset of the activity period and hyperglycemia are correlated with an increased sympathetic tonus, we investigated whether this autonomic branch is involved in the SCN control of plasma glucose rhythm and liver rhythmicity. Interestingly, hepatic sympathectomy combined with a six-meal feeding schedule resulted in a disruption of the plasma glucose rhythmicity without affecting the daily variation in clock-gene mRNA expression in the liver. Taking all these data together, we conclude that (i) the SCN needs the sympathetic pathway to the liver to generate the 24-h rhythm in plasma glucose concentrations, (ii) rhythmic clock-gene expression in the liver is not dependent on the sympathetic liver innervation and (iii) clock-gene rhythmicity in liver cells is not sufficient for sustaining a circadian rhythm in plasma glucose concentrations.
authors.affiliation: Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands. c.cailotto@nih.knaw.nl
authors.forename: Cathy
authors.initials: C
authors.lastname: Cailotto
authors.forename: Susanne E
authors.initials: SE
authors.lastname: La Fleur
authors.forename: Caroline
authors.initials: C
authors.lastname: Van Heijningen
authors.forename: Joke
authors.initials: J
authors.lastname: Wortel
authors.forename: Andries
authors.initials: A
authors.lastname: Kalsbeek
authors.forename: Matthijs
authors.initials: M
authors.lastname: Feenstra
authors.forename: Paul
authors.initials: P
authors.lastname: Pévet
authors.forename: Ruud M
authors.initials: RM
authors.lastname: Buijs
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D001786:Blood Glucose / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000097:blood; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D004435:Eating / Q000502:physiology; D004594:Electrophysiology; D006128:Growth / Q000502:physiology; D007328:Insulin / Q000097:blood; D008099:Liver / Q000294:innervation* / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000502:physiology; D010507:Periodicity; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013493:Suprachiasmatic Nucleus / Q000502:physiology*; D013562:Sympathectomy
chemical_list: D001786:Blood Glucose; D018076:DNA, Complementary; D007328:Insulin; D012313:RNA; D003345:Corticosterone