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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 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]
Experimental — accuracy not yet measuredIn the citing paper
“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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Cites
The nuclear receptor superfamily: the second decade
Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90199-x · Cited by 6,964
Coordination of circadian timing in mammals
Reppert, S. M., & Weaver, D. R. (2002) · Nature · doi:10.1038/nature00965 · Cited by 4,379
Role of leptin in the neuroendocrine response to fasting
Ahima, R. S., Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos-Flier, E., & Flier, J. S. (1996) · Nature · doi:10.1038/382250a0 · Cited by 3,117
Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice
Turek, F. W., Joshu, C., Kohsaka, A., Lin, E., Ivanova, G., McDearmon, E., Laposky, A., Losee-Olson, S., Easton, A., Jensen, D. R., et al. (2005) · Science · doi:10.1126/science.1108750 · Cited by 2,485
Abnormal splicing of the leptin receptor in diabetic mice
Lee, G.-H., Proenca, R., Montez, J. M., Carroll, K. M., Darvishzadeh, J. G., Lee, J. I., & Friedman, J. M. (1996) · Nature · doi:10.1038/379632a0 · Cited by 2,327
Chen, H., Charlat, O., Tartaglia, L. A., Woolf, E. A., Weng, X., Ellis, S. J., Lakey, N. D., Culpepper, J., More, K. J., Breitbart, R. E., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81294-5 · Cited by 2,214
Phinney, D. G., & Prockop, D. J. (2007) · Stem Cells · doi:10.1634/stemcells.2007-0637 · Cited by 1,910
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
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
STEROID RECEPTOR REGULATED TRANSCRIPTION OF SPECIFIC GENES AND GENE NETWORKS
Yamamoto, K. R. (1985) · Annual Review of Genetics · doi:10.1146/annurev.ge.19.120185.001233 · Cited by 1,850
Self-citationMechanisms involved in the side effects of glucocorticoids
SCHACKE, H. (2002) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(02)00297-8 · Cited by 1,847
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
A transgenic model of visceral obesity and the metabolic syndrome
Masuzaki, H., Paterson, J., Shinyama, H., Morton, N. M., Mullins, J. J., Seckl, J. R., & Flier, J. S. (2001) · Science · doi:10.1126/science.1066285 · Cited by 1,766
Molecular components of the mammalian circadian clock
Ko, C. H., & Takahashi, J. S. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl207 · Cited by 1,725
High-Fat Diet Disrupts Behavioral and Molecular Circadian Rhythms in Mice
Kohsaka, A., Laposky, A. D., Ramsey, K. M., Estrada, C., Joshu, C., Kobayashi, Y., Turek, F. W., & Bass, J. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.006 · Cited by 1,528
Genome-wide analysis of estrogen receptor binding sites
Carroll, J. S., Meyer, C. A., Song, J. S., Li, W., Geistlinger, T., Eeckhoute, J., Brodsky, A. S., Keeton, E. K., Fertuck, K. C., Hall, G., et al. (2006) · Nature Genetics · doi:10.1038/ng1901 · Cited by 1,397
Rudic, R. D., McNamara, P., Curtis, A.-M., Boston, R. C., Panda, S., Hogenesch, J. B., & FitzGerald, G. A. (2004) · PLoS Biology · doi:10.1371/journal.pbio.0020377 · Cited by 1,059
Nuclear Receptor Expression Links the Circadian Clock to Metabolism
Yang, X., Downes, M., Yu, R. T., Bookout, A. L., He, W., Straume, M., Mangelsdorf, D. J., & Evans, R. M. (2006) · Cell · doi:10.1016/j.cell.2006.06.050 · Cited by 946
Differential Functions of mPer1, mPer2, and mPer3 in the SCN Circadian Clock
Bae, K., Jin, X., Maywood, E. S., Hastings, M. H., Reppert, S. M., & Weaver, D. R. (2001) · Neuron · doi:10.1016/s0896-6273(01)00302-6 · Cited by 905
Schwartz, M. W., Baskin, D. G., Bukowski, T. R., Kuijper, J. L., Foster, D., Lasser, G., Prunkard, D. E., Porte, D., Woods, S. C., Seeley, R. J., et al. (1996) · Diabetes · doi:10.2337/diab.45.4.531 · Cited by 904 · cited 1×
“However, other studies have demonstrated that elevated leptin levels improve insulin sensitivity and glucose tolerance (36, 37) and that leptin resistance causes obesity and diabetes (38, 39).”
BackgroundNonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock.
Zheng, B., Albrecht, U., Kaasik, K., Sage, M., Lu, W., Vaishnav, S., Li, Q., Sun, Z. S., Eichele, G., Bradley, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00380-4 · Cited by 900
Kotelevtsev, Y. V., Holmes, M. C., Burchell, A. N., Houston, P., Schmoll, D., Jamieson, P. M., Best, R., Brown, R., Edwards, C. R. W., Seckl, J. R., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.26.14924 · Cited by 863
Feast and Famine: Critical Role of Glucocorticoids with Insulin in Daily Energy Flow
Dallman, M. F., Strack, A. M., Akana, S. F., Bradbury, M. J., Hanson, E. S., Scribner, K. A., & Smith, M. (1993) · Frontiers in Neuroendocrinology · doi:10.1006/frne.1993.1010 · Cited by 796 · cited 1×
“Thus, because cycling of glucocorticoid secretion is modified by feeding times, glucocorticoid levels are highest during fasting when blood sugar is lowest (6).”
BackgroundNocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects.
Sinha, M. K., Ohannesian, J. P., Heiman, M. L., Kriauciunas, A., Stephens, T. W., Magosin, S., Marco, C. C., & Caro, J. F. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118551 · Cited by 780
Warrell, R. P., de Thé, H., Wang, Z.-Y., & Degos, L. (1993) · New England Journal of Medicine · doi:10.1056/nejm199307153290307 · Cited by 778
He, L.-Z., de Figueiredo‐Pontes, L. L., Rego, E. M., & Pandolfi, P. P. (2015) · Springer eBooks · doi:10.1007/978-3-662-46875-3_63 · Cited by 766
Lecker, S. H., Solomon, V., Mitch, W. E., & Goldberg, A. L. (1999) · Journal of Nutrition · doi:10.1093/jn/129.1.227s · Cited by 742
The mPer2 gene encodes a functional component of the mammalian circadian clock
Zheng, B., Larkin, D. W., Albrecht, U., Sun, Z. S., Sage, M., Eichele, G., Lee, C. C., & Bradley, A. (1999) · Nature · doi:10.1038/22118 · Cited by 718
Rev-erbα, a Heme Sensor That Coordinates Metabolic and Circadian Pathways
Yin, L., Wu, N., Curtin, J. C., Qatanani, M., Szwergold, N. R., Reid, R. A., Waitt, G. M., Parks, D. J., Pearce, K. H., Wisely, G. B., et al. (2007) · Science · doi:10.1126/science.1150179 · Cited by 707
Direct antidiabetic effect of leptin through triglyceride depletion of tissues
Shimabukuro, M., Koyama, K., Chen, G., Wang, M.-Y., Trieu, F., Lee, Y., Newgard, C. B., & Unger, R. H. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4637 · Cited by 646
Transcriptional coactivator PGC-1α integrates the mammalian clock and energy metabolism
Liu, C., Li, S., Liu, T., Borjigin, J., & Lin, J. D. (2007) · Nature · doi:10.1038/nature05767 · Cited by 643
Interchromosomal Interactions and Olfactory Receptor Choice
Lomvardas, S., Barnea, G., Pisapia, D. J., Mendelsohn, M. M., Kirkland, J., & Axel, R. (2006) · Cell · doi:10.1016/j.cell.2006.06.035 · Cited by 641
Human Leptin Levels Are Pulsatile and Inversely Related to Pituitary–Ardenal Function
Licinio, J., Mantzoros, C., Negrão, A. B., Cizza, G., Wong, M.-L., Bongiorno, P. B., Chrousos, G. P., Karp, B., Allen, C., Flier, J. S., et al. (1997) · Nature Medicine · doi:10.1038/nm0597-575 · Cited by 632
The Molecular Clock Mediates Leptin-Regulated Bone Formation
Fu, L., Patel, M. S., Bradley, A., Wagner, E. F., & Karsenty, G. (2005) · Cell · doi:10.1016/j.cell.2005.06.028 · Cited by 590
Light activates the adrenal gland: Timing of gene expression and glucocorticoid release
Ishida, A., Mutoh, T., Ueyama, T., Bando, H., Masubuchi, S., Nakahara, D., Tsujimoto, G., & Okamura, H. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.009 · Cited by 589
Characterization of the normal temporal pattern of plasma corticosteroid levels.
KRIEGER, D. T., ALLEN, W., RIZZO, F., & KRIEGER, H. P. (1971) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-32-2-266 · Cited by 549
The UCSC Genome Browser Database: 2008 update
Karolchik, D., Kuhn, R. M., Baertsch, R., Barber, G. P., Clawson, H., Diekhans, M., Giardine, B. M., Harte, R., Hinrichs, A. S., Hsu, F., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm966 · Cited by 525
Mechanisms of glucocorticoid-induced myopathy
Schakman, O., Gilson, H., & Thissen, J. P. (2008) · Journal of Endocrinology · doi:10.1677/joe-07-0606 · Cited by 521
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 480
Masuzaki, H., Yamamoto, H., Kenyon, C. J., Elmquist, J. K., Morton, N. M., Paterson, J. M., Shinyama, H., Sharp, M. G. F., Fleming, S., Mullins, J. J., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17845 · Cited by 434
Cell- and gene-specific regulation of primary target genes by the androgen receptorPreprint
Bolton, E. C., So, A. Y., Chaivorapol, C., Haqq, C. M., Li, H., & Yamamoto, K. R. (2007) · Genes & Development · doi:10.1101/gad.1564207 · Cited by 348
Self-citationYamamoto, T., Nakahata, Y., Tanaka, M., Yoshida, M., Soma, H., Shinohara, K., Yasuda, A., Mamine, T., & Takumi, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509600200 · Cited by 309
Determinants of Cell- and Gene-Specific Transcriptional Regulation by the Glucocorticoid Receptor
So, A. Y., Chaivorapol, C., Bolton, E. C., Li, H., & Yamamoto, K. R. (2007) · PLoS Genetics · doi:10.1371/journal.pgen.0030094 · Cited by 304
Self-citationCircadian clocks: setting time by food
Mendoza, J. (2007) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2006.01510.x · Cited by 257
Abe, K., Kroning, J., Greer, M. A., & CRITCHLOW, V. (2008) · Neuroendocrinology · doi:10.1159/000122913 · Cited by 189
Masuzaki, H., & Flier, J. S. (2003) · Current Drug Targets - Immune Endocrine & Metabolic Disorders · doi:10.2174/1568008033340135 · Cited by 98
Gounarides, J., Korach-André, M., Killary, K. A., Argentieri, G. J., Turner, O., & Laurent, D. (2007) · Endocrinology · doi:10.1210/en.2007-1214 · Cited by 90
So, A. Y., Cooper, S., Feldman, B. J., Manuchehri, M., & Yamamoto, K. R. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801551105 · Cited by 82
Self-citationFood and the circadian activity of the hypothalamic-pituitary-adrenal axis
Leal, A. M. O., & Moreira, A. C. (1997) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x1997001200003 · Cited by 60
Glucocorticoid use in rheumatoid arthritis: benefits, mechanisms, and risks.
Townsend, H. B., & Saag, K. G. (2004) · PubMed · Cited by 47
Fighting Fat with Muscle: Bulking Up to Slim Down
Harrison, B. C., & Leinwand, L. A. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.01.003 · Cited by 19
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Mohawk, J. A., Green, C. B., & Takahashi, J. S. (2012) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-060909-153128 · Cited by 2,265
Circadian integration of metabolism and energetics
Bass, J., & Takahashi, J. S. (2010) · Science · doi:10.1126/science.1195027 · Cited by 1,910
Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis
Thaiss, C. A., Zeevi, D., Levy, M., Zilberman-Schapira, G., Suez, J., Tengeler, A. C., Abramson, L., Katz, M. N., Korem, T., Zmora, N., et al. (2014) · Cell · doi:10.1016/j.cell.2014.09.048 · Cited by 1,449
“Of note, glucose tolerance by itself underlies circadian variation (Kaasik et al., 2013; So et al., 2009).”
BackgroundCircadian rhythms, sleep, and metabolism
Huang, W., Ramsey, K. M., Marcheva, B., & Bass, J. T. (2011) · Journal of Clinical Investigation · doi:10.1172/jci46043 · Cited by 749
Circadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures
Potter, G. D., Skene, D. J., Arendt, J., Cade, J. E., Grant, P. J., & Hardie, L. J. (2016) · Endocrine Reviews · doi:10.1210/er.2016-1083 · Cited by 781
“Some clock genes are directly regulated by glucocorticoids via glucocorticoid response elements (103).”
Metadata
- 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 › Endocrinology › 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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