http://purl.uniprot.org/citations/29530977 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/29530977 | http://www.w3.org/2000/01/rdf-schema#comment | "Hepatic gluconeogenesis is essential to maintain blood glucose levels, and its abnormal activation leads to hyperglycemia and type 2 diabetes. However, the molecular mechanisms in the regulation of hepatic gluconeogenesis remain to be fully defined. In this study, using murine hepatocytes and a liver-specific knockout mouse model, we explored the physiological role of nuclear factor Y (NF-Y) in regulating hepatic glucose metabolism and the underlying mechanism. We found that NF-Y targets the gluconeogenesis pathway in the liver. Hepatic NF-Y expression was effectively induced by cAMP, glucagon, and fasting in vivo Lentivirus-mediated NF-Y overexpression in Hepa1-6 hepatocytes markedly raised the gluconeogenic gene expression and cellular glucose production compared with empty vector control cells. Conversely, CRISPR/Cas9-mediated knockdown of NF-Y subunit A (NF-YA) attenuated gluconeogenic gene expression and glucose production. We also provide evidence indicating that CRE-loxP-mediated, liver-specific NF-YA knockout compromises hepatic glucose production. Mechanistically, luciferase reporter gene assays and ChIP analysis indicated that NF-Y activates transcription of the gluconeogenic genes Pck1 and G6pc, by encoding phosphoenolpyruvate carboxykinase (PEPCK) and the glucose-6-phosphatase catalytic subunit (G6Pase), respectively, via directly binding to the CCAAT regulatory sequence motif in their promoters. Of note, NF-Y enhanced gluconeogenesis by interacting with cAMP-responsive element-binding protein (CREB). Overall, our results reveal a previously unrecognized physiological function of NF-Y in controlling glucose metabolism by up-regulating the gluconeogenic genes Pck1 and G6pc Modulation of hepatic NF-Y expression may therefore offer an attractive therapeutic approach to manage type 2 diabetes."xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra117.000508"xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/author | "Chen J."xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/author | "Chen Y."xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/author | "Liu Y.'"xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/author | "Su Z."xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/author | "Zhang Y."xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/author | "Zhang Y.'"xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/author | "Guan Q."xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/pages | "7894-7904"xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/title | "Regulation of hepatic gluconeogenesis by nuclear factor Y transcription factor in mice."xsd:string |
http://purl.uniprot.org/citations/29530977 | http://purl.uniprot.org/core/volume | "293"xsd:string |
http://purl.uniprot.org/citations/29530977 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29530977 |
http://purl.uniprot.org/citations/29530977 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29530977 |
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