ArticleDiabetes2014
Cyclin D1 represses gluconeogenesis via inhibition of the transcriptional coactivator PGC1α.
Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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
35 citing papers in PubMed, 57 citations in OpenAlex.
- Cyclin D1 regulates the hepatic response to feeding: Evidence for non-cell cycle roles in the liver.bioRxiv : the preprint server for biology · 2026Article
- Multidimensional Regulatory Mechanisms and Targeted Therapeutic Strategies for Inhibited Keratinocyte Proliferation in Diabetic Wounds.Drug design, development and therapy · 2026Review
- Cord Blood Exosomal miRNAs from Small-for-Gestational-Age Newborns: Association with Measures of PostnatalInternational journal of molecular sciences · 2025Article
- Cyclin D1 extensively reprograms metabolism to support biosynthetic pathways in hepatocytes.The Journal of biological chemistry · 2023Article
- The mechanistic target of rapamycin complex 1 pathway involved in hepatic gluconeogenesis through peroxisome-proliferator-activated receptor γ coactivator-1Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2022Article
- Cell cycle on the crossroad of tumorigenesis and cancer therapy.Trends in cell biology · 2022Review
- Liver fat metabolism of broilers regulated byFrontiers in microbiology · 2022Article
- Hepatic Gadd45β promotes hyperglycemia and glucose intolerance through DNA demethylation of PGC-1α.The Journal of experimental medicine · 2021Article
- Linking metabolic dysfunction with cardiovascular diseases: Brn-3b/POU4F2 transcription factor in cardiometabolic tissues in health and disease.Cell death & disease · 2021Review
- CDK2 limits the highly energetic secretory program of mature β cells by restricting PEP cycle-dependent KCell reports · 2021Article
- Review
- DHA Suppresses Hepatic Lipid AccumulationFrontiers in nutrition · 2021Article
- MEK inhibition reprograms CD8Nature immunology · 2021Article
- Cyclin D degradation by E3 ligases in cancer progression and treatment.Seminars in cancer biology · 2020Review
- Article
- A negative reciprocal regulatory axis between cyclin D1 and HNF4α modulates cell cycle progression and metabolism in the liver.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The double dealing of cyclin D1.Cell cycle (Georgetown, Tex.) · 2020Review
- Effects of the Bone/Bone Marrow Microenvironments on Prostate Cancer Cells and CD59 Expression.BioMed research international · 2020Article
- Recent advances with cyclin-dependent kinase inhibitors: therapeutic agents for breast cancer and their role in immuno-oncology.Expert review of anticancer therapy · 2019Review
- Evidence for a Novel Regulatory Interaction Involving Cyclin D1, Lipid Droplets, Lipolysis, and Cell Cycle Progression in Hepatocytes.Hepatology communications · 2019Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Hepatic gluconeogenesis is crucial to maintain normal blood glucose during periods of nutrient deprivation. Gluconeogenesis is controlled at multiple levels by a variety of signal transduction and transcriptional pathways. However, dysregulation of these pathways leads to hyperglycemia and type 2 diabetes. While the effects of various signaling pathways on gluconeogenesis are well established, the downstream signaling events repressing gluconeogenic gene expression are not as well understood. The cell-cycle regulator cyclin D1 is expressed in the liver, despite the liver being a quiescent tissue. The most well-studied function of cyclin D1 is activation of cyclin-dependent kinase 4 (CDK4), promoting progression of the cell cycle. We show here a novel role for cyclin D1 as a regulator of gluconeogenic and oxidative phosphorylation (OxPhos) gene expression. In mice, fasting decreases liver cyclin D1 expression, while refeeding induces cyclin D1 expression. Inhibition of CDK4 enhances the gluconeogenic gene expression, whereas cyclin D1-mediated activation of CDK4 represses the gluconeogenic gene-expression program in vitro and in vivo. Importantly, we show that cyclin D1 represses gluconeogenesis and OxPhos in part via inhibition of peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) activity in a CDK4-dependent manner. Indeed, we demonstrate that PGC1α is novel cyclin D1/CDK4 substrate. These studies reveal a novel role for cyclin D1 on metabolism via PGC1α and reveal a potential link between cell-cycle regulation and metabolic control of glucose homeostasis.
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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.