ArticlePloS one2016
Glucose Alters Per2 Rhythmicity Independent of AMPK, Whereas AMPK Inhibitor Compound C Causes Profound Repression of Clock Genes and AgRP in mHypoE-37 Hypothalamic Neurons.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Role of O-GlcNAcylation in Central Nervous System Development and Injuries: A Systematic Review.Molecular neurobiology · 2024Pooled it
- Small-Molecule Kinase Inhibitors Modulating Circadian Rhythms.Medicinal research reviews · 2026Review
- Timing of food intake, chrononutritional behavior patterns, and risk of metabolic syndrome in the French NutriNet-Santé cohort.Scientific reports · 2026Article
- Review
- SnRK1 stimulates the histone H3K27me3 demethylase JMJ705 to regulate a transcriptional switch to control energy homeostasis.The Plant cell · 2021Article
- Review
- Metformin selectively dampens the acute inflammatory response through an AMPK-dependent mechanism.Scientific reports · 2021Article
- A Double Negative Feedback Loop between mTORC1 and AMPK Kinases Guarantees Precise Autophagy Induction upon Cellular Stress.International journal of molecular sciences · 2019Article
- The circadian regulation of food intake.Nature reviews. Endocrinology · 2019Review
- Bisphenol A Alters Bmal1, Per2, and Rev-Erba mRNA and Requires Bmal1 to Increase Neuropeptide Y Expression in Hypothalamic Neurons.Endocrinology · 2019Article
- Identification of a novel 2-oxindole fluorinated derivative as in vivo antitumor agent for prostate cancer acting via AMPK activation.Scientific reports · 2018Article
- A Free-Choice High-Fat High-Sugar Diet Alters Day-NightFrontiers in endocrinology · 2018Article
- Flexible clock systems: adjusting the temporal programme.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- Development of diabetes does not alter behavioral and molecular circadian rhythms in a transgenic rat model of type 2 diabetes mellitus.American journal of physiology. Endocrinology and metabolism · 2017Article
- Inhibition of expression of the circadian clock gene Period causes metabolic abnormalities including repression of glycometabolism in Bombyx mori cells.Scientific reports · 2017Article
- Functional characterization of AMP-activated protein kinase signaling in tumorigenesis.Biochimica et biophysica acta · 2016Review
- Cancer Clocks Out for Lunch: Disruption of Circadian Rhythm and Metabolic Oscillation in Cancer.Frontiers in cell and developmental biology · 2016Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Specific neurons in the hypothalamus are regulated by peripheral hormones and nutrients to maintain proper metabolic control. It is unclear if nutrients can directly control clock gene expression. We have therefore utilized the immortalized, hypothalamic cell line mHypoE-37, which exhibits robust circadian rhythms of core clock genes. mHypoE-37 neurons were exposed to 0.5 or 5.5 mM glucose, comparable to physiological levels in the brain. Per2 and Bmal1 mRNAs were assessed every 3 hours over 36 hours. Incubation with 5.5 mM glucose significantly shortened the period and delayed the phase of Per2 mRNA levels, but had no effect on Bmal1. Glucose had no significant effect on phospho-GSK3β, whereas AMPK phosphorylation was altered. Thus, the AMPK inhibitor Compound C was utilized, and mRNA levels of Per2, Bmal1, Cryptochrome1 (Cry1), agouti-related peptide (AgRP), carnitine palmitoyltransferase 1C (Cpt1c), and O-linked N-acetylglucosamine transferase (Ogt) were measured. Remarkably, Compound C dramatically reduced transcript levels of Per2, Bmal1, Cry1, and AgRP, but not Cpt1c or Ogt. Because AMPK was not inhibited at the same time or concentrations as the clock genes, we suggest that the effect of Compound C on gene expression occurs through an AMPK-independent mechanism. The consequences of inhibition of the rhythmic expression of clock genes, and in turn downstream metabolic mediators, such as AgRP, could have detrimental effects on overall metabolic processes. Importantly, the effects of the most commonly used AMPK inhibitor Compound C should be interpreted with caution, considering its role in AMPK-independent repression of specific genes, and especially clock gene rhythm dysregulation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.