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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6852
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pubmed:dateCreated |
2001-9-14
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pubmed:abstractText |
Blood glucose levels are maintained by the balance between glucose uptake by peripheral tissues and glucose secretion by the liver. Gluconeogenesis is strongly stimulated during fasting and is aberrantly activated in diabetes mellitus. Here we show that the transcriptional coactivator PGC-1 is strongly induced in liver in fasting mice and in three mouse models of insulin action deficiency: streptozotocin-induced diabetes, ob/ob genotype and liver insulin-receptor knockout. PGC-1 is induced synergistically in primary liver cultures by cyclic AMP and glucocorticoids. Adenoviral-mediated expression of PGC-1 in hepatocytes in culture or in vivo strongly activates an entire programme of key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase, leading to increased glucose output. Full transcriptional activation of the PEPCK promoter requires coactivation of the glucocorticoid receptor and the liver-enriched transcription factor HNF-4alpha (hepatic nuclear factor-4alpha) by PGC-1. These results implicate PGC-1 as a key modulator of hepatic gluconeogenesis and as a central target of the insulin-cAMP axis in liver.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix Leucine...,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Nuclear Factor 4,
http://linkedlifedata.com/resource/pubmed/chemical/Hormones,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoenolpyruvate Carboxykinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid,
http://linkedlifedata.com/resource/pubmed/chemical/Tcfl4 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/peroxisome-proliferator-activated...
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0028-0836
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pubmed:author |
pubmed-author:AdelmantGG,
pubmed-author:ChenGG,
pubmed-author:DonovanJJ,
pubmed-author:GrannerD KDK,
pubmed-author:KahnC RCR,
pubmed-author:NewgardC BCB,
pubmed-author:PualA KAK,
pubmed-author:PuigserverPP,
pubmed-author:SpiegelmanB MBM,
pubmed-author:StaffordJJ,
pubmed-author:WuZZ,
pubmed-author:YoonJ CJC
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pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
413
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
131-8
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11557972-3T3 Cells,
pubmed-meshheading:11557972-Amino Acid Motifs,
pubmed-meshheading:11557972-Animals,
pubmed-meshheading:11557972-Basic Helix-Loop-Helix Leucine Zipper Transcription Factors,
pubmed-meshheading:11557972-Blood Glucose,
pubmed-meshheading:11557972-Cell Line,
pubmed-meshheading:11557972-Cyclic AMP,
pubmed-meshheading:11557972-DNA-Binding Proteins,
pubmed-meshheading:11557972-Diabetes Mellitus, Experimental,
pubmed-meshheading:11557972-Fasting,
pubmed-meshheading:11557972-Gluconeogenesis,
pubmed-meshheading:11557972-Hepatocyte Nuclear Factor 4,
pubmed-meshheading:11557972-Hormones,
pubmed-meshheading:11557972-Insulin,
pubmed-meshheading:11557972-Liver,
pubmed-meshheading:11557972-Male,
pubmed-meshheading:11557972-Mice,
pubmed-meshheading:11557972-Mice, Knockout,
pubmed-meshheading:11557972-Obesity,
pubmed-meshheading:11557972-Phosphoenolpyruvate Carboxykinase (GTP),
pubmed-meshheading:11557972-Phosphoproteins,
pubmed-meshheading:11557972-RNA, Messenger,
pubmed-meshheading:11557972-Rats,
pubmed-meshheading:11557972-Rats, Wistar,
pubmed-meshheading:11557972-Receptor, Insulin,
pubmed-meshheading:11557972-Receptors, Glucocorticoid,
pubmed-meshheading:11557972-Response Elements,
pubmed-meshheading:11557972-Transcription Factors,
pubmed-meshheading:11557972-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1.
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pubmed:affiliation |
Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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