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.
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The SCN needs an intact sympathetic innervation of the liver to generate a daily rhythm in plasma glucose concentrations.
“From these studies it became clear that the SCN does indeed need an intact sympathetic innervation of the liver to generate a daily rhythm in plasma glucose concentrations [63,66].”
From Circadian control of glucose metabolism (2014) · cites this paper as [66]
Cites
Damiola, F., Le Minh, N., Preitner, N., Kornmann, B., Fleury-Olela, F., & Schibler, U. (2000) · Genes & Development · doi:10.1101/gad.183500 · Cited by 2,394 · see citing works
Yoo, S.-H., Yamazaki, S., Lowrey, P. L., Shimomura, K., Ko, C. H., Buhr, E. D., Siepka, S. M., Hong, H.-K., Oh, W. J., Yoo, O. J., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308709101 · Cited by 2,329 · see citing works
Resetting central and peripheral circadian oscillators in transgenic rats
Yamazaki, S., Numano, R., Abe, M., Hida, A., Takahashi, R.-I., Ueda, M., Block, G. D., Sakaki, Y., Menaker, M., & Tei, H. (2000) · Science · doi:10.1126/science.288.5466.682 · Cited by 1,907 · see citing works
Resetting of circadian time in peripheral tissues by glucocorticoid signaling
Balsalobre, A., Brown, S. A., Marcacci, L., Tronche, F., Kellendonk, C., Reichardt, H. M., Schütz, G., & Schibler, U. (2000) · Science · doi:10.1126/science.289.5488.2344 · Cited by 1,859 · see citing works
Entrainment of the circadian clock in the liver by feeding
Stokkan, K.-A., Yamazaki, S., Tei, H., Sakaki, Y., & Menaker, M. (2001) · Science · doi:10.1126/science.291.5503.490 · Cited by 1,800 · see citing works
Extensive and divergent circadian gene expression in liver and heart
Storch, K.-F., Lipan, O., Leykin, I., Viswanathan, N., Davis, F. C., Wong, W. H., & Weitz, C. J. (2002) · Nature · doi:10.1038/nature744 · Cited by 1,509 · see citing works
Molecular analysis of mammalian circadian rhythms
Reppert, S. M., & Weaver, D. R. (2001) · Annual Review of Physiology · doi:10.1146/annurev.physiol.63.1.647 · Cited by 1,444 · see citing works
Control Mechanism of the Circadian Clock for Timing of Cell Division in Vivo
Matsuo, T., Yamaguchi, S., Mitsui, S., Emi, A., Shimoda, F., & Okamura, H. (2003) · Science · doi:10.1126/science.1086271 · Cited by 1,132 · see citing works
Zylka, M. J., Shearman, L. P., Weaver, D. R., & Reppert, S. M. (1998) · Neuron · doi:10.1016/s0896-6273(00)80492-4 · Cited by 865 · see citing works
Hypothalamic KATP channels control hepatic glucose production
Pocai, A., Lam, T. K. T., Gutierrez-Juarez, R., Obici, S., Schwartz, G. J., Bryan, J., Aguilar-Bryan, L., & Rossetti, L. (2005) · Nature · doi:10.1038/nature03439 · Cited by 645 · see citing works
Hypothalamic integration of central and peripheral clocks
Buijs, R. M., & Kalsbeek, A. (2001) · Nature reviews. Neuroscience · doi:10.1038/35081582 · Cited by 580 · see citing works
Self-citationRestricted feeding entrains liver clock without participation of the suprachiasmatic nucleus
Hara, R., Wan, K., Wakamatsu, H., Aida, R., Moriya, T., Akiyama, M., & Shibata, S. (2001) · Genes to Cells · doi:10.1046/j.1365-2443.2001.00419.x · Cited by 569 · cited 2× · see citing works
“001) in accordance with data previously described in mouse and rat (Zylka et al., 1998; Damiola et al., 2000; Hara et al., 2001; Miki et al., 2003; Yamamoto et al., 2004).”
ResultInfluentialPeripheral Circadian Oscillators in Mammals: Time and Food
Schibler, U., Ripperger, J. A., & Brown, S. A. (2003) · Journal of Biological Rhythms · doi:10.1177/0748730403018003007 · Cited by 525 · see citing works
Steffens, A. B. (1969) · Physiology & Behavior · doi:10.1016/0031-9384(69)90126-7 · Cited by 499 · see citing works
Glucocorticoid hormones inhibit food‐induced phase‐shifting of peripheral circadian oscillators
Minh, N. L., Damiola, F., Tronche, F., Schütz, G., & Schibler, U. (2001) · The EMBO Journal · doi:10.1093/emboj/20.24.7128 · Cited by 467 · see citing works
Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis
Lam, T. K. T., Pocai, A., Gutierrez-Juarez, R., Obici, S., Bryan, J., Aguilar-Bryan, L., Schwartz, G. J., & Rossetti, L. (2005) · Nature Medicine · doi:10.1038/nm1201 · Cited by 432 · see citing works
Buijs, R. M., van Eden, C. G., Goncharuk, V. D., & Kalsbeek, A. (2003) · Journal of Endocrinology · doi:10.1677/joe.0.1770017 · Cited by 387 · see citing works
Self-citationPhotic Induction of mPer1 and mPer2 in Cry -Deficient Mice Lacking a Biological Clock
Okamura, H., Miyake, S., Sumi, Y., Yamaguchi, S., Yasui, A., Muijtjens, M., Hoeijmakers, J. H. J., & van der Horst, G. T. J. (1999) · Science · doi:10.1126/science.286.5449.2531 · Cited by 375 · see citing works
Transcriptional oscillation of canonical clock genes in mouse peripheral tissues
Yamamoto, T., Nakahata, Y., Soma, H., Akashi, M., Mamine, T., & Takumi, T. (2004) · BMC Molecular Biology · doi:10.1186/1471-2199-5-18 · Cited by 308 · see citing works
The Suprachiasmatic Nucleus Generates the Diurnal Changes in Plasma Leptin Levels
Kalsbeek, A., Fliers, E., Romijn, J. A., la Fleur, S. E., Wortel, J., Bakker, O., Endert, E., & Buijs, R. M. (2001) · Endocrinology · doi:10.1210/endo.142.6.8197 · Cited by 305 · see citing works
Self-citationA noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo
Yoo, S. H., Ko, C. H., Lowrey, P. L., Buhr, E. D., Song, E.-J., Chang, S., Yoo, O. J., Yamazaki, S., Lee, C., & Takahashi, J. S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409763102 · Cited by 299 · see citing works
Adrenergic regulation of clock gene expression in mouse liver
Terazono, H., Mutoh, T., Yamaguchi, S., Kobayashi, M., Akiyama, M., Udo, R., Ohdo, S., Okamura, H., & Shibata, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0936797100 · Cited by 293 · see citing works
Kalsbeek, A., & Buijs, R. M. (2002) · Cell and Tissue Research · doi:10.1007/s00441-002-0577-0 · Cited by 261 · see citing works
Self-citationResetting Mechanism of Central and Peripheral Circadian Clocks in Mammals
Hirota, T., & Fukada, Y. (2004) · ZOOLOGICAL SCIENCE · doi:10.2108/zsj.21.359 · Cited by 260 · see citing works
Differential control of peripheral circadian rhythms by suprachiasmatic-dependent neural signals
Guo, H., Brewer, J. M., Champhekar, A. S., Harris, R. B. S., & Bittman, E. L. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409734102 · Cited by 258 · see citing works
A Suprachiasmatic Nucleus Generated Rhythm In Basal Glucose Concentrations
Fleur, L., Kalsbeek, Wortel, & Buijs (1999) · Journal of Neuroendocrinology · doi:10.1046/j.1365-2826.1999.00373.x · Cited by 256 · see citing works
Kalsbeek, A., La Fleur, S., Van Heijningen, C., & Buijs, R. M. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5328-03.2004 · Cited by 244 · see citing works
Self-citationRuiter, M., La Fleur, S. E., van Heijningen, C., van der Vliet, J., Kalsbeek, A., & Buijs, R. M. (2003) · Diabetes · doi:10.2337/diabetes.52.7.1709 · Cited by 170 · see citing works
Self-citationla Fleur, S. E., Kalsbeek, A., Wortel, J., & Buijs, R. M. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02423-9 · Cited by 160 · see citing works
Self-citationCircadian Control of Insulin Secretion Is Independent of the Temporal Distribution of Feeding
Kalsbeek, A., & Strubbe, J. H. (1998) · Physiology & Behavior · doi:10.1016/s0031-9384(97)00493-9 · Cited by 142 · see citing works
Self-citationCentral and peripheral circadian oscillator mechanisms in flies and mammals
Glossop, N. R. J., & Hardin, P. E. (2002) · Journal of Cell Science · doi:10.1242/jcs.115.17.3369 · Cited by 120 · see citing works
Kudo, T., Akiyama, M., Kuriyama, K., Sudo, M., Moriya, T., & Shibata, S. (2004) · Diabetologia · doi:10.1007/s00125-004-1461-0 · Cited by 110 · see citing works
Cryptochrome-Deficient Mice Lack Circadian Electrical Activity in the Suprachiasmatic Nuclei
Albus, H., Bonnefont, X., Chaves, I., Yasui, A., Doczy, J., van der Horst, G. T. J., & Meijer, J. H. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00923-5 · Cited by 108 · see citing works
Reciprocal Innervation of the Liver: Its Significance in Metabolic Control
Shimazu, T. (1983) · Advances in metabolic disorders · doi:10.1016/b978-0-12-027310-2.50019-0 · Cited by 89 · see citing works
The mammalian circadian clock: a network of gene expression
Albrecht, U. (2004) · Frontiers in bioscience · doi:10.2741/1196 · Cited by 86 · see citing works
Daily Rhythms in Glucose Metabolism: Suprachiasmatic Nucleus Output to Peripheral Tissue
la Fleur, S. (2003) · Journal of neuroendocrinology · doi:10.1046/j.1365-2826.2003.01019.x · Cited by 86 · see citing works
SCN: Ringmaster of the Circadian Circus or Conductor of the Circadian Orchestra?
Davidson, A. J., Yamazaki, S., & Menaker, M. (2003) · Novartis Foundation symposium · doi:10.1002/0470090839.ch9 · Cited by 78 · see citing works
Food-anticipatory activity and liver per1-luc activity in diabetic transgenic rats
Davidson, A. J., Stokkan, K., Yamazaki, S., & Menaker, M. (2002) · Physiology & Behavior · doi:10.1016/s0031-9384(02)00680-7 · Cited by 59 · see citing works
Electrical stimulation of the suprachiasmatic nucleus of the hypothalamus causes hyperglycemia
Nagai, K., Fujii, T., Inoue, S., Takamura, Y., & Nakagawa, H. (1988) · Hormone and Metabolic Research · doi:10.1055/s-2007-1010743 · Cited by 59 · see citing works
Bardsley, W. G., Bukhari, N., Ferguson, M. W. J., et al. (1995) · Computers & Chemistry · doi:10.1016/0097-8485(95)00007-f · Cited by 58 · see citing works
Total parenteral nutrition entrains the central and peripheral circadian clocks
Miki, H., Yano, M., Iwanaga, H., et al. (2003) · Neuroreport · doi:10.1097/00001756-200308060-00010 · Cited by 29 · see citing works
Lang, C. H. (1995) · Brain Research Bulletin · doi:10.1016/0361-9230(95)00052-g · Cited by 28 · see citing works
Autoregulation of Glucose Production
Tappy, L., Jéquier, E., & Schneiter, P. (2000) · Physiology · doi:10.1152/physiologyonline.2000.15.4.198 · Cited by 22 · see citing works
Strey, C. H., Young, J. M., Collier, M., et al. (2005) · Diabetologia · doi:10.1007/s00125-005-1782-7 · Cited by 3 · see citing works
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- Authors
- Cailotto, C., La Fleur, S. E., Van Heijningen, C., Wortel, J., Kalsbeek, A., Feenstra, M., Pévet, P., & Buijs, R. M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Cailotto, Cathy
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2005-11
- Volume
- 22
- Issue
- 10
- Pages
- 2531-2540
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2020343018
- Cited by
- 191
- References
- 44
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 7 · 2021: 12 · 2020: 8 · 2019: 7 · 2018: 9 · 2017: 10 · 2016: 11 · 2015: 13 · 2014: 10 · 2013: 13 · 2012: 18
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- suprachiasmatic nucleus, circadian rhythm, plasma glucose, clock genes, hyperglycemia
- MeSH terms
- Animals, Autonomic Nervous System, Blood Glucose, Chromatography, High Pressure Liquid, Corticosterone, Eating, Electrophysiology, Growth, Insulin, Liver, Male, Motor Activity, Periodicity, RNA, Suprachiasmatic Nucleus, Sympathectomy, Rats, Wistar, DNA, Complementary, Reverse Transcriptase Polymerase Chain Reaction, Rats
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