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MicroRNA 33 Regulates Glucose Metabolism
Open accessAbstract
Metabolic diseases are characterized by the failure of regulatory genes or proteins to effectively orchestrate specific pathways involved in the control of many biological processes. In addition to the classical regulators, recent discoveries have shown the remarkable role of small noncoding RNAs (microRNAs [miRNAs]) in the posttranscriptional regulation of gene expression. In this regard, we have recently demonstrated that miR-33a and miR33b, intronic miRNAs located within the sterol regulatory element-binding protein (SREBP) genes, regulate lipid metabolism in concert with their host genes. Here, we show that miR-33b also cooperates with SREBP1 in regulating glucose metabolism by targeting phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC), key regulatory enzymes of hepatic gluconeogenesis. Overexpression of miR-33b in human hepatic cells inhibits PCK1 and G6PC expression, leading to a significant reduction of glucose production. Importantly, hepatic SREBP1c/miR-33b levels correlate inversely with the expression of PCK1 and G6PC upon glucose infusion in rhesus monkeys. Taken together, these results suggest that miR-33b works in concert with its host gene to ensure a fine-tuned regulation of lipid and glucose homeostasis, highlighting the clinical potential of miR-33a/b as novel therapeutic targets for a range of metabolic diseases.
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“SRC1 was up-regulated in miR-33bKI mice and it was opposite to the results of previous report14.”
From MicroRNA-33b knock-in mice for an intron of sterol regulatory element-binding factor 1 (Srebf1) exhibit reduced HDL-C in vivo (2014) · cites this paper as [14]
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Metadata
- Authors
- Ramírez, C. M., Goedeke, L., Rotllan, N., Yoon, J.-H., Cirera-Salinas, D., Mattison, J. A., Suárez, Y., de Cabo, R., Gorospe, M., & Fernández-Hernando, C.
- Affiliations
- New York University (US)
- Departments of Medicine and Cell Biology, Leon H. Charney Division of Cardiology and Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, New York, USA
- National Institutes of Health (US)
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2013-08-01
- Volume
- 33
- Issue
- 15
- Pages
- 2891-2902
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC3719675
- OpenAlex
- W2148995089
- Cited by
- 154
- References
- 46
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 5 · 2023: 12 · 2022: 8 · 2021: 19 · 2020: 12 · 2019: 11 · 2018: 15 · 2017: 16 · 2016: 18 · 2015: 14 · 2014: 13 · 2013: 1
- FWCI
- 5.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (F31AG043318)
- National Heart, Lung, and Blood Institute (R01HL105945, R01HL106063, R01HL107953)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- miR-33b, miR-33a, SREBP-1c, SREBP1, glucose metabolism, gluconeogenesis, PCK1, glucose-6-phosphatase, hepatic glucose production, post-transcriptional regulation, lipid metabolism, metabolic disorders, therapeutic target
- MeSH terms
- Animals, Gene Expression Regulation, Gluconeogenesis, Glucose, Glucose-6-Phosphatase, Glycogen, Humans, Macaca mulatta, Male, Phosphoenolpyruvate Carboxykinase (GTP), Hepatocytes, MicroRNAs, Intracellular Signaling Peptides and Proteins, Sterol Regulatory Element Binding Protein 1, Hep G2 Cells
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