Glucocorticoid regulation of the circadian clock modulates glucose homeostasis
Open accessAbstract
Circadian clock genes are regulated by glucocorticoids; however, whether this regulation is a direct or secondary effect and the physiological consequences of this regulation were unknown. Here, we identified glucocorticoid response elements (GREs) at multiple clock genes and showed that 3 were directly regulated by the glucocorticoid receptor. We determined that a GRE within the core clock gene Per2 was continuously occupied during rhythmic expression and essential for glucocorticoid regulation of that gene in vivo. We further demonstrated that mice with a genomic deletion spanning this GRE expressed elevated leptin levels and were protected from glucose intolerance and insulin resistance on glucocorticoid treatment but not from muscle wasting. We conclude that Per2 is an integral component of a particular glucocorticoid regulatory pathway and that glucocorticoid regulation of the peripheral clock is selectively required for some actions of glucocorticoids.
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Resetting of the peripheral clock occurs through molecular mechanisms involving direct interaction of glucocorticoids, glucocorticoid response elements and regulatory regions of core clock genes Bmal1, Cry1, Per1 and Per2.
“Resetting of the peripheral clock occurs through well-defined molecular mechanisms that involve direct interaction of glucocorticoids, glucocorticoid response elements and the regulatory regions of core clock genes Bmal1, Cry1, Per1 and Per2 [63, 64].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [64]
The Results report GR occupancy at response elements near Per1 and Per2 and identify them as direct GR targets involved in regulating the peripheral clock (page not provided). Bmal1 and Cry1 also showed glucocorticoid-stimulated oscillation, but the paper does not identify direct GR interaction with response elements at those genes; it reports that other clock genes did not change detectably in the early-response test. (LLM, conf=0.89)
Experimental — accuracy not yet measuredPer2 null mice exhibit no glucocorticoid oscillations, indicating that PER2 may impact glucocorticoid receptor-dependent glucose metabolism.
“Per2 null mice exhibit no glucocorticoid oscillations, indicating that PER2 may also impact glucocorticoid receptor (GR)-dependent glucose metabolism [24,25].”
From Circadian control of glucose metabolism (2014) · cites this paper as [24]
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“Functional glucocorticoid response elements (GREs) in the promoter regions of Per1, Per2, and E4bp4 have also been reported as possible factors in the signaling mechanisms of molecular clocks [26, 27], and the expression of Rev-erba in the liver has been reported to decrease in response to glucocorticoid treatment via…”
BackgroundMongrain, V., Hernández, S., Pradervand, S., Dorsaz, S., Curie, T., Hagiwara, G., Gip, P., Heller, H. C., & Franken, P. (2010) · SLEEP · doi:10.1093/sleep/33.9.1147 · Cited by 197 · see citing works
Shimba, A., Cui, G., Tani‐ichi, S., Ogawa, M., Abe, S., Okazaki, F., Kitano, S., Miyachi, H., Yamada, H., Hara, T., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.01.004 · Cited by 187 · see citing works
“, 2011), and GRs induce transcription of the Nfil3 gene by binding to its promoter (So et al., 2009).”
BackgroundInfluentialCircadian endocrine rhythms: the hypothalamic–pituitary–adrenal axis and its actions
Nicolaides, N. C., Charmandari, E., Chrousos, G. P., & Kino, T. (2014) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12464 · Cited by 183 · see citing works
Control of immunity by glucocorticoids in health and disease
Shimba, A., & Ikuta, K. (2020) · Seminars in Immunopathology · doi:10.1007/s00281-020-00827-8 · Cited by 184 · see citing works
Homeostasis of Glucose and Lipid in Non-Alcoholic Fatty Liver Disease
Chao, H., Chao, S.-W., Lin, H., Ku, H., & Cheng, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020298 · Cited by 184 · see citing works
“Moreover, induction of Per2 by glucocorticoids was demonstrated to affect glucose metabolism in mice with hyperglycemic conditions which are protected from glucose intolerance as lose of glucocorticoid response element in the Per2 promoter [118].”
BackgroundArcher, S. N., & Oster, H. (2015) · Journal of Sleep Research · doi:10.1111/jsr.12307 · Cited by 171 · see citing works
Clock Genes and Clock-Controlled Genes in the Regulation of Metabolic Rhythms
Mazzoccoli, G., Pazienza, V., & Vinciguerra, M. (2012) · Chronobiology International · doi:10.3109/07420528.2012.658127 · Cited by 171 · see citing works
“In this manner, the integration of circadian clock circuitry control and glucose homeostasis regulation by glucocorticoids might confer selective advantage by ensuring a coupling of activity and feeding (So et al., 2009).”
BackgroundBlood transcriptome based biomarkers for human circadian phase
Laing, E., Möller‐Levet, C. S., Poh, N., Santhi, N., Archer, S. N., & Dijk, D. (2017) · eLife · doi:10.7554/elife.20214 · Cited by 161 · see citing works
Logan, R. W., Edgar, N. M., Gillman, A. G., Hoffman, D., Zhu, X., & McClung, C. A. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.01.011 · Cited by 154 · see citing works
The role of the circadian clock system in physiology
Pilorz, V., Helfrich‐Förster, C., & Oster, H. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-2103-y · Cited by 156 · see citing works
“Finally, GCs can alter the methylation patterns of other genes [96] and regulate expression of clock genes, hence acting as a synchronizing factor of the circadian system [145].”
Nicolaides, N. C., Charmandari, E., Kino, T., & Chrousos, G. P. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00070 · Cited by 149 · see citing works
“Therefore, Per1 and Per2 genes are upregulated, causing a phase delay of the peripheral clocks, but not the SCN master clock (67).”
BackgroundSleep and circadian regulation of cortisol: A short review
O'Byrne, N. A., Yuen, F., Butt, W. Z., & Liu, P. Y. (2021) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2021.03.011 · Cited by 145 · see citing works
The circadian clock and glucocorticoids – interactions across many time scales
Dickmeis, T., Weger, B. D., & Weger, M. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.05.012 · Cited by 144 · see citing works
“GR binding to an intronic sequence of the Per2 gene has also been described (So et al., 2009), and the Rev-ERBa and RORa genes have been shown to contain a functional negative GRE element (Surjit et al., 2011; Torra et al., 2000) (Fig.”
The cost of circadian desynchrony: Evidence, insights and open questions
West, A. C., & Bechtold, D. A. (2015) · BioEssays · doi:10.1002/bies.201400173 · Cited by 143 · see citing works
“Compellingly, one of those rhythmic factors unaffected by the loss of the hepatic clock was Per2; perhaps not surprising, given that the Per2 promoter contains many non-circadian regulatory elements responsive to systemic signalling factors such as glucocorticoid and serum response factor [41, 42].”
BackgroundCircadian Clocks, Stress, and Immunity
Dumbell, R., Matveeva, O., & Oster, H. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00037 · Cited by 143 · see citing works
“GRE are present in the promoter region of the clock genes Per1, Per2, Npas2, and various clock controlled genes involved in the synchronization of peripheral circadian rhythms (17).”
BackgroundCharmandari, E., Chrousos, G. P., Lambrou, G. I., Pavlaki, A., Koide, H., Ng, S. S. M., & Kino, T. (2011) · PLoS ONE · doi:10.1371/journal.pone.0025612 · Cited by 139 · see citing works
“It is also known that glucocorticoids influence the circadian CLOCK system by affecting expression levels of some of its components [22].”
BackgroundThe adrenal peripheral clock: Glucocorticoid and the circadian timing system
Son, G. H., Chung, S., & Kim, K. (2011) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2011.07.003 · Cited by 136 · see citing works
“Although Per2 gene expression was not induced in the liver by an acute application of GC [213], a recent study has argued that constant GR occupancy of an intronic binding site of the Per2 gene is crucial for its cyclic expression in certain cell types [187], implying the presence of cell-type specific regulatory mech…”
Diurnal Regulation of Lipid Metabolism and Applications of Circadian Lipidomics
Gooley, J. J., & Chua, E. C.-P. (2014) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2014.04.001 · Cited by 136 · see citing works
Metabolic control through glucocorticoid hormones: An update
Rose, A. J., & Herzig, S. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.03.007 · Cited by 133 · see citing works
Wu, W., Zhou, T., Berliner, A., Banerjee, P., & Zhou, S. (2010) · Angewandte Chemie International Edition · doi:10.1002/anie.201001508 · Cited by 133 · see citing works
Entrainment of the mouse circadian clock by sub-acute physical and psychological stress
Tahara, Y., Shiraishi, T., Kikuchi, Y., Haraguchi, A., Kuriki, D., Sasaki, H., Motohashi, H., Sakai, T., & Shibata, S. (2015) · Scientific Reports · doi:10.1038/srep11417 · Cited by 128 · see citing works
Glucose Oxidase-Instructed Fluorescence Amplification Strategy for Intracellular Glucose Detection
Jiang, S., Zhang, Y., Yang, Y., Huang, Y., Ma, G., Luo, Y., Huang, P., & Lin, J. (2019) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.9b00010 · Cited by 129 · see citing works
Chronobesity: role of the circadian system in the obesity epidemic
Laermans, J., & Depoortere, I. (2015) · Obesity Reviews · doi:10.1111/obr.12351 · Cited by 126 · see citing works
Metabolic rivalry: circadian homeostasis and tumorigenesis
Kinouchi, K., & Sassone‐Corsi, P. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-0291-9 · Cited by 125 · see citing works
Watson, M. L., Baehr, L. M., Reichardt, H. M., Tuckermann, J. P., Bodine, S. C., & Furlow, J. D. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00512.2011 · Cited by 120 · see citing works
“Since glucocorticoids have been linked to circadian changes in peripheral clock activity and metabolism (2, 49), we monitored voluntary wheel running activity in GR and MGRKO for 30 days.”
Glucocorticoids Regulate Circadian Rhythm of Innate and Adaptive Immunity
Shimba, A., & Ikuta, K. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.02143 · Cited by 121 · see citing works
“The Nfil3 gene locus contains a GRE motif (6), and its expression is reduced in GR-deficient T cells in the early phase of Th2 differentiation.”
BackgroundSamarasinghe, R. A., Di Maio, R., Volonte, D., Galbiati, F., Lewis, M., Romero, G., & DeFranco, D. B. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102821108 · Cited by 120 · see citing works
“Moreover, recent findings suggest that even transient GC exposure can influence the periodic (circadian and/or ultradian) expression of certain GR target genes (36, 37).”
BackgroundImpaired Glucocorticoid Production and Response to Stress in Arntl-Deficient Male Mice
Leliavski, A., Shostak, A., Husse, J., & Oster, H. (2013) · Endocrinology · doi:10.1210/en.2013-1531 · Cited by 120 · see citing works
Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm
Cheon, S., Park, N., Cho, S., & Kim, K. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt307 · Cited by 119 · see citing works
“Consistent with the results of the ChIP assay, GBS-mediated luciferase activities were increased by DEX treatment in WT and Bmal1 / MEFs (Supplementary Figure S4).”
BackgroundMethodInfluentialAdrenal Clocks and the Role of Adrenal Hormones in the Regulation of Circadian Physiology
Leliavski, A., Dumbell, R., Ott, V., & Oster, H. (2014) · Journal of Biological Rhythms · doi:10.1177/0748730414553971 · Cited by 119 · see citing works
“Such external and internal misalignment is associated with several health disorders, and GC rhythms play an important role in this context due to their capacity to reset tissue clocks via GR signaling (Balsalobre et al., 2000; So et al., 2009; Lamia et al., 2011) (Figure 2B).”
BackgroundCistromic Reprogramming of the Diurnal Glucocorticoid Hormone Response by High-Fat Diet
Quagliarini, F., Mir, A. A., Balázs, K., Wierer, M., Dyar, K. A., Jouffe, C., Makris, K., Hawe, J. S., Heinig, M., Filipp, F. V., et al. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.10.007 · Cited by 117 · see citing works
“Several studies have shown both genetic and physical interactions between GR and the core clock machinery; functional GREs have been identified in the Per1 and Per2 regulatory regions, while the Rev-erbα promoter was found to be repressed by GR (So et al., 2009; Torra et al., 2000; Yamamoto et al., 2005).”
BackgroundSpencer, R. L., Chun, L. E., Hartsock, M. J., & Woodruff, E. R. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.12.005 · Cited by 113 · see citing works
Entrainment of the mouse circadian clock: Effects of stress, exercise, and nutrition
Tahara, Y., & Shibata, S. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.12.026 · Cited by 116 · see citing works
“Because the glucocorticoid receptor is not expressed in the SCN, the effects of glucocorticoids on the circadian clock can be observed in other areas of the brain, including the amygdala, peripheral tissues, and cultured fibroblasts [49-54].”
BackgroundHomeostatic and circadian contribution to EEG and molecular state variables of sleep regulation
Curie, T., Mongrain, V., Dorsaz, S., Mang, G. M., Emmenegger, Y., & Franken, P. (2013) · SLEEP · doi:10.5665/sleep.2440 · Cited by 94 · see citing works
Nuclear receptors rock around the clock
Zhao, X., Cho, H., Yu, R. T., Atkins, A. R., Downes, M., & Evans, R. M. (2014) · EMBO Reports · doi:10.1002/embr.201338271 · Cited by 108 · see citing works
“This observation is supported by the identification of glucocorticoid response elements (GREs) in several clock genes, including Per1 and Per2 , suggesting that GR is a critical regulator for clock gene expression at the molecular level [9].”
Sasaki, H., Hattori, Y., Ikeda, Y., Kamagata, M., Iwami, S., Yasuda, S., Tahara, Y., & Shibata, S. (2016) · Scientific Reports · doi:10.1038/srep27607 · Cited by 104 · see citing works
Chun, L. E., Woodruff, E. R., Morton, S. J., Hinds, L. R., & Spencer, R. L. (2015) · Journal of Biological Rhythms · doi:10.1177/0748730415598608 · Cited by 103 · see citing works
“The timing/entrainment of these rhythms may be related to the presence of a glucocorticoid response element (GRE) and cAMP response element in the promoter region of both genes (Colwell, 2011; So et al., 2009; T. Yamamoto et al., 2005).”
BackgroundHPA Axis Interactions with Behavioral Systems
Packard, A. E. B., Egan, A. E., & Ulrich‐Lai, Y. M. (2016) · Comprehensive physiology · doi:10.1002/cphy.c150042 · Cited by 130 · see citing works
Fujihara, Y., Kondo, H., Noguchi, T., & Togari, A. (2014) · Bone · doi:10.1016/j.bone.2013.12.026 · Cited by 96 · see citing works
van de Peppel, J., Strini, T., Tilburg, J., Westerhoff, H. V., van Wijnen, A. J., & van Leeuwen, J. P. T. M. (2017) · Stem Cell Reports · doi:10.1016/j.stemcr.2017.02.018 · Cited by 93 · see citing works
Circadian blueprint of metabolic pathways in the brain
Greco, C. M., & Sassone‐Corsi, P. (2018) · Nature reviews. Neuroscience · doi:10.1038/s41583-018-0096-y · Cited by 93 · see citing works
Glucocorticoid receptor modulators
Meijer, O. C., Koorneef, L. L., & Kroon, J. (2018) · Annales d Endocrinologie · doi:10.1016/j.ando.2018.03.004 · Cited by 93 · see citing works
Circadian Synchrony: Sleep, Nutrition, and Physical Activity
Healy, K. L., Morris, A. R., & Liu, A. C. (2021) · Frontiers in Network Physiology · doi:10.3389/fnetp.2021.732243 · Cited by 90 · see citing works
“BMAL1/CLOCK activity is negatively regulated by transcriptional repressors PERIOD (PER1/2/3) and CRYPTOCHROME (CRY1/2) (Sato et al., 2006; Takahashi, 2017).”
InfluentialCircadian control of pain and neuroinflammation
Segal, J. P., Tresidder, K. A., Bhatt, C., Gilron, I., & Ghasemlou, N. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24150 · Cited by 89 · see citing works
Circadian Clocks and Inflammation: Reciprocal Regulation and Shared Mediators
Cermakian, N., Westfall, S., & Kießling, S. (2014) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-014-0286-x · Cited by 88 · see citing works
“LPS administration suppresses the expression of Per1 and Per2 in the liver (Okada et al. 2008).”
BackgroundInfluentialMultilevel Interactions of Stress and Circadian System: Implications for Traumatic Stress
Agorastos, A., Nicolaides, N. C., Bozikas, V. P., Chrousos, G. P., & Pervanidou, P. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.01003 · Cited by 89 · see citing works
Circadian regulation of mitochondrial uncoupling and lifespan
Ulgherait, M., Chen, A., McAllister, S. F., Kim, H. X., Delventhal, R., Wayne, C. R., Garcia, C., Recinos, Y., Oliva, M. K., Canman, J. C., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-15617-x · Cited by 89 · see citing works
Clinical reviews in allergy and immunology
Leung, D. Y. M., Ledford, D. K., Wechsler, M. E., Fulkerson, P. C., Bochner, B. S., Gauvreau, G. M., Gleich, G. J., Henkel, T., Kolbeck, R., Mathur, S. K., et al. (2012) · Cited by 87 · see citing works
Liquid Crystal Monomer: A Potential PPARγ Antagonist
Zhao, H., Li, C., Naik, M. Y., Wu, J., Cardilla, A., Liu, M., Zhao, F., Snyder, S. A., Xia, Y. F., Su, G., et al. (2023) · Environmental Science & Technology · doi:10.1021/acs.est.2c08109 · Cited by 86 · see citing works
Circadian Rhythm Gene Period 3 Is an Inhibitor of the Adipocyte Cell Fate
Costa, M. J. D. C., So, A. Y., Kaasik, K., Krueger, K. C., Pillsbury, M. L., Fu, Y., Ptáček, L. J., Yamamoto, K. R., & Feldman, B. J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.164558 · Cited by 83 · see citing works
Self-citationThe circadian clock, metabolism and obesity
Albrecht, U. (2017) · Obesity Reviews · doi:10.1111/obr.12502 · Cited by 83 · see citing works
“This suggests that GR is a critical regulator of clock gene expression (52).”
BackgroundSleep, testosterone and cortisol balance, and ageing men
Liu, P. Y., & Reddy, R. T. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-022-09755-4 · Cited by 80 · see citing works
“Resetting of the peripheral clock occurs through well-defined molecular mechanisms that involve direct interaction of glucocorticoids, glucocorticoid response elements and the regulatory regions of core clock genes Bmal1, Cry1, Per1 and Per2 [63, 64].”
BackgroundRole of the Circadian Clock in the Metabolic Syndrome and Nonalcoholic Fatty Liver Disease
Shetty, A., Hsu, J. W., Manka, P. P., & Syn, W. (2018) · Digestive Diseases and Sciences · doi:10.1007/s10620-018-5242-x · Cited by 82 · see citing works
Nakamura, Y., Harama, D., Shimokawa, N., Hara, M., Suzuki, R., Tahara, Y., Ishimaru, K., Katoh, R., Okumura, K., Ogawa, H., et al. (2011) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2011.02.006 · Cited by 79 · see citing works
Hoyt, K. R., & Obrietan, K. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00537-9 · Cited by 77 · see citing works
“The process by which rhythmic release of GC drives clock gene rhythms appears to be mediated, at least in part, via a transcriptional mechanism in which GC drives glucocorticoid responsive element- (GRE) mediated expression of core clock genes [55].”
BackgroundEndocrine regulation of circadian rhythms
Begemann, K., Rawashdeh, O., Olejniczak, I., Pilorz, V., de Assis, L. V. M., Osorio-Mendoza, J., & Oster, H. (2025) · npj Biological Timing and Sleep · doi:10.1038/s44323-025-00024-6 · Cited by 77 · see citing works
“However, several clock genes also contain glucocorticoid response elements 23 .”
Entrainment of peripheral clock genes by cortisol
Mavroudis, P. D., Scheff, J. D., Calvano, S. E., Lowry, S. F., & Androulakis, I. P. (2012) · Physiological Genomics · doi:10.1152/physiolgenomics.00001.2012 · Cited by 76 · see citing works
Human studies on hypothalamo-pituitary-adrenal (HPA) axis
Liyanarachchi, K., Ross, R. J. M., & Debono, M. (2017) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2017.10.011 · Cited by 78 · see citing works
Nutrition, metabolism, and epigenetics: pathways of circadian reprogramming
Sato, T., & Sassone‐Corsi, P. (2022) · EMBO Reports · doi:10.15252/embr.202152412 · Cited by 74 · see citing works
“The promoter region of Per contains a GR-binding region, and Per gene expression rapidly increases after GR activation (Yamamoto et al , 2005; So et al , 2009).”
Circadian Variation in Placental and Hepatic Clock Genes in Rat Pregnancy
Wharfe, M. D., Mark, P. J., & Waddell, B. J. (2011) · Endocrinology · doi:10.1210/en.2011-0081 · Cited by 74 · see citing works
“Previous studies in vitro show that dexamethasone up-regulates Per2 expression in mesenchymal stem cells (25) and all three Per genes and Cry1 in fibroblasts (26).”
BackgroundGabarre, P., Loens, C., Tamzali, Y., Barrou, B., Jaisser, F., & Tourret, J. (2021) · American Journal of Transplantation · doi:10.1111/ajt.16836 · Cited by 72 · see citing works
Per2 Mutation Recapitulates the Vascular Phenotype of Diabetes in the Retina and Bone Marrow
Bhatwadekar, A. D., Yan, Y., Qi, X., Thinschmidt, J. S., Neu, M. B., Calzi, S. L., Shaw, L. C., Dominiguez, J. M., Busik, J. V., Lee, C., et al. (2012) · Diabetes · doi:10.2337/db12-0172 · Cited by 69 · see citing works
“Per2 is an important component of the glucocorticoid regulatory pathway, and disruption of glucocorticoid regulation and leptin regulation may be partly responsible for the enhanced glucose sensitivity observed in the Per2 mutant mice (26).”
BackgroundGetting rhythm: how do babies do it?
Joseph, D., Chong, N. W., Shanks, M. E., Rosato, E., Taub, N. A., Petersen, S. A., Symonds, M. E., Whitehouse, W. P., & Wailoo, M. P. (2014) · Archives of Disease in Childhood Fetal & Neonatal · doi:10.1136/archdischild-2014-306104 · Cited by 67 · see citing works
Functional Organization of Neuronal and Humoral Signals Regulating Feeding Behavior
Schwartz, G. J., & Zeltser, L. M. (2013) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071812-161125 · Cited by 67 · see citing works
“The Per2 gene has GC-responsive elements in its promoter; eliminating them abolishes CORT’s effects on glucose homeostasis and leptin levels (115).”
Cedernaes, J., Lampola, L., Axelsson, E. K., Liethof, L., Hassanzadeh, S., Yeganeh, A., Broman, J., Schiöth, H. B., & Benedict, C. (2015) · Journal of Sleep Research · doi:10.1111/jsr.12340 · Cited by 67 · see citing works
Komoto, S., Kondo, H., Fukuta, O., & Togari, A. (2012) · Chronobiology International · doi:10.3109/07420528.2011.636496 · Cited by 65 · see citing works
“Other groups also reported that glucocorticoid synchronizes circadian rhythms in gene expression in some cell types (Balsalobre et al., 1998; Burioka et al., 2005; Fujioka et al., 2006; Reddy et al., 2007; So et al., 2009).”
BackgroundCircadian Clocks Make Metabolism Run
Sinturel, F., Petrenko, V., & Dibner, C. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.01.018 · Cited by 64 · see citing works
Chronic mild stress alters circadian expressions of molecular clock genes in the liver
Takahashi, K., Yamada, T., Tsukita, S., Kaneko, K., Shirai, Y., Munakata, Y., Ishigaki, Y., Imai, J., Uno, K., Hasegawa, Y., et al. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00388.2012 · Cited by 63 · see citing works
“In vitro studies have demonstrated that 347 glucocorticoids stimulate the transcriptional rhythmicities of Per1 (5), NPAS2 (45), 348 Cry1 (5), Bmal1 and Clock (36), all of which were found to show altered oscillations in 349 the present study.”
BackgroundInfluentialPantazopoulos, H., Wiseman, J. T., Markota, M., Ehrenfeld, L., & Berretta, S. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.04.006 · Cited by 64 · see citing works
“also directly regulate CLOCK genes through glucocorticoid response elements located in the promoter region of Per1 and Per2 genes (142, 143).”
Lechasseur, A., Jubinville, É., Routhier, J., Bérubé, J., Hamel-Auger, M., Talbot, M., Lamothe, J., Aubin, S., Paré, M., Beaulieu, M., et al. (2017) · Physiological Reports · doi:10.14814/phy2.13440 · Cited by 63 · see citing works
“Glucose metabolism (Panda et al. 2002; So et al. 2009; Bass and Takahashi 2010), immune and inflammatory responses (Oishi et al.”
Background
- Authors
- So, A. Y.-L., Bernal, T. U., Pillsbury, M. L., Yamamoto, K. R., & Feldman, B. J.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-10-13
- Volume
- 106
- Issue
- 41
- Pages
- 17582-17587
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2757402
- OpenAlex
- W1998522501
- Cited by
- 431
- References
- 51
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 37 · 2023: 19 · 2022: 36 · 2021: 28 · 2020: 32 · 2019: 28 · 2018: 22 · 2017: 28 · 2016: 33 · 2015: 23 · 2014: 25 · 2013: 20 · 2012: 18
- FWCI
- 8.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- National Cancer Institute (CA20535, R01CA020535, R37CA020535)
- National Institute of General Medical Sciences (R25GM056847, GM 56847)
- National Institute of Diabetes and Digestive and Kidney Diseases (K08DK073697, DK73697)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- glucocorticoids, circadian clock, clock genes, glucocorticoid response element, glucocorticoid receptor, Per2, glucose homeostasis, insulin resistance, impaired glucose tolerance, leptin, muscle atrophy, peripheral clocks
- MeSH terms
- Animals, Circadian Rhythm, Gene Expression Regulation, Glucocorticoids, Glucose, Homeostasis, Nuclear Proteins, Transcription Factors, Transcription, Genetic, Polymerase Chain Reaction, Cell Cycle Proteins, Leptin, Mice, Period Circadian Proteins, Mesenchymal Stem Cells
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