PER2 promotes glucose storage to liver glycogen during feeding and acute fasting by inducing Gys2 PTG and GL expression
Open accessAbstract
The interplay between hepatic glycogen metabolism and blood glucose levels is a paradigm of the rhythmic nature of metabolic homeostasis. Here we show that mice lacking a functional PER2 protein (Per2 (Brdm1) ) display reduced fasting glycemia, altered rhythms of hepatic glycogen accumulation, and altered rhythms of food intake. Per2 (Brdm1) mice show reduced hepatic glycogen content and altered circadian expression during controlled fasting and refeeding. Livers from Per2 (Brdm1) mice display reduced glycogen synthase protein levels during refeeding, and increased glycogen phosphorylase activity during fasting. The latter is explained by PER2 action on the expression of the adapter proteins PTG and GL, which target the protein phosphatase-1 to glycogen to decrease glycogen phosphorylase activity. Finally, PER2 interacts with genomic regions of Gys2, PTG, and G L . These results indicate an important role for PER2 in the hepatic transcriptional response to feeding and acute fasting that promotes glucose storage to liver glycogen.
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Per2 mutant mice show reduced fasting glycemia, loss of rhythmic glycogen accumulation in the liver, elevated plasma insulin levels and impaired gluconeogenesis.
“Per2 mutant mice show reduced fasting glycemia, a loss of rhythmic glycogen accumulation in the liver, elevated plasma insulin levels and impaired gluconeogenesis [20–22]”
From Circadian control of glucose metabolism (2014) · cites this paper as [21]
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- Authors
- Zani, F., Breasson, L., Becattini, B., Vukolic, A., Montani, J.-P., Albrecht, U., Provenzani, A., Ripperger, J. A., & Solinas, G.
- Affiliations
- University of Fribourg (CH)
- University of Trento (IT)
- Corresponding author
- Solinas, Giovanni
- ORCID
- Venue
- Molecular Metabolism
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 2
- Issue
- 3
- Pages
- 292-305
- ISSN
- 2212-8778 (ISSN-L)
- PMC
- PMC3773838
- OpenAlex
- W2014234042
- Cited by
- 75
- References
- 35
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 10 · 2021: 4 · 2020: 9 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 10 · 2015: 11 · 2014: 2
- FWCI
- 4.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecular Metabolism (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion, cc-by-nc-nd)
- Funders
- Swiss National Science Foundation (31003A-118172, 31003A_135684)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Keywords
- Per2, liver glycogen, glycogen synthase, glycogen phosphorylase, GL, protein phosphatase 1, circadian clock, fasting, refeeding, glucose storage, circadian gene expression
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