Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
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 stron...
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| Veröffentlicht in: | Nature (London) 2001-09, Vol.413 (6852), p.131-138 |
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| creator | Spiegelman, Bruce M Yoon, J. Cliff Puigserver, Pere Chen, Guoxun Donovan, Jerry Wu, Zhidan Rhee, James Adelmant, Guillaume Stafford, John Kahn, C. Ronald Granner, Daryl K Newgard, Christopher B |
| description | 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. |
| doi_str_mv | 10.1038/35093050 |
| format | Article |
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Cliff ; Puigserver, Pere ; Chen, Guoxun ; Donovan, Jerry ; Wu, Zhidan ; Rhee, James ; Adelmant, Guillaume ; Stafford, John ; Kahn, C. Ronald ; Granner, Daryl K ; Newgard, Christopher B</creator><creatorcontrib>Spiegelman, Bruce M ; Yoon, J. Cliff ; Puigserver, Pere ; Chen, Guoxun ; Donovan, Jerry ; Wu, Zhidan ; Rhee, James ; Adelmant, Guillaume ; Stafford, John ; Kahn, C. Ronald ; Granner, Daryl K ; Newgard, Christopher B</creatorcontrib><description>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.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/35093050</identifier><identifier>PMID: 11557972</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing</publisher><subject>3T3 Cells ; Amino Acid Motifs ; Animals ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Biological and medical sciences ; Blood ; Blood Glucose - metabolism ; Cell Line ; Cyclic AMP - metabolism ; Diabetes ; Diabetes Mellitus, Experimental - blood ; Diabetes Mellitus, Experimental - metabolism ; DNA-Binding Proteins ; Fasting ; Fundamental and applied biological sciences. Psychology ; Gluconeogenesis ; Glucose ; hepatic nuclear factor-4^a ; Hepatocyte Nuclear Factor 4 ; Hormones - metabolism ; Insulin ; Insulin - physiology ; Lipids. Glycolipids ; Liver ; Liver - metabolism ; Male ; Metabolisms and neurohumoral controls ; Mice ; Mice, Knockout ; Obesity - genetics ; Obesity - metabolism ; PGC-1 protein ; Phosphoenolpyruvate Carboxykinase (GTP) - genetics ; Phosphoenolpyruvate Carboxykinase (GTP) - metabolism ; Phosphoproteins - metabolism ; Rats ; Rats, Wistar ; Receptor, Insulin - genetics ; Receptor, Insulin - metabolism ; Receptors, Glucocorticoid - metabolism ; Response Elements ; RNA, Messenger - metabolism ; Rodents ; Tissues ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transcription Factors - physiology ; Tumor Cells, Cultured ; Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><ispartof>Nature (London), 2001-09, Vol.413 (6852), p.131-138</ispartof><rights>2001 INIST-CNRS</rights><rights>COPYRIGHT 2001 Nature Publishing Group</rights><rights>Copyright Macmillan Journals Ltd. Sep 13, 2001</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c527t-2e52cdf269e4c6fc4d7369cb43e4174a6e0c0d62b84d4425601cf60ccecbd4383</citedby><cites>FETCH-LOGICAL-c527t-2e52cdf269e4c6fc4d7369cb43e4174a6e0c0d62b84d4425601cf60ccecbd4383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,2728,27929,27930</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1135974$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11557972$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Spiegelman, Bruce M</creatorcontrib><creatorcontrib>Yoon, J. Cliff</creatorcontrib><creatorcontrib>Puigserver, Pere</creatorcontrib><creatorcontrib>Chen, Guoxun</creatorcontrib><creatorcontrib>Donovan, Jerry</creatorcontrib><creatorcontrib>Wu, Zhidan</creatorcontrib><creatorcontrib>Rhee, James</creatorcontrib><creatorcontrib>Adelmant, Guillaume</creatorcontrib><creatorcontrib>Stafford, John</creatorcontrib><creatorcontrib>Kahn, C. Ronald</creatorcontrib><creatorcontrib>Granner, Daryl K</creatorcontrib><creatorcontrib>Newgard, Christopher B</creatorcontrib><title>Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1</title><title>Nature (London)</title><addtitle>Nature</addtitle><description>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.</description><subject>3T3 Cells</subject><subject>Amino Acid Motifs</subject><subject>Animals</subject><subject>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors</subject><subject>Biological and medical sciences</subject><subject>Blood</subject><subject>Blood Glucose - metabolism</subject><subject>Cell Line</subject><subject>Cyclic AMP - metabolism</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Experimental - blood</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>DNA-Binding Proteins</subject><subject>Fasting</subject><subject>Fundamental and applied biological sciences. 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Cliff ; Puigserver, Pere ; Chen, Guoxun ; Donovan, Jerry ; Wu, Zhidan ; Rhee, James ; Adelmant, Guillaume ; Stafford, John ; Kahn, C. 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Cliff</au><au>Puigserver, Pere</au><au>Chen, Guoxun</au><au>Donovan, Jerry</au><au>Wu, Zhidan</au><au>Rhee, James</au><au>Adelmant, Guillaume</au><au>Stafford, John</au><au>Kahn, C. Ronald</au><au>Granner, Daryl K</au><au>Newgard, Christopher B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1</atitle><jtitle>Nature (London)</jtitle><addtitle>Nature</addtitle><date>2001-09-13</date><risdate>2001</risdate><volume>413</volume><issue>6852</issue><spage>131</spage><epage>138</epage><pages>131-138</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>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.</abstract><cop>London</cop><pub>Nature Publishing</pub><pmid>11557972</pmid><doi>10.1038/35093050</doi><tpages>8</tpages></addata></record> |
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| ispartof | Nature (London), 2001-09, Vol.413 (6852), p.131-138 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_743148739 |
| source | MEDLINE; Nature Journals Online; Alma/SFX Local Collection |
| subjects | 3T3 Cells Amino Acid Motifs Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Biological and medical sciences Blood Blood Glucose - metabolism Cell Line Cyclic AMP - metabolism Diabetes Diabetes Mellitus, Experimental - blood Diabetes Mellitus, Experimental - metabolism DNA-Binding Proteins Fasting Fundamental and applied biological sciences. Psychology Gluconeogenesis Glucose hepatic nuclear factor-4^a Hepatocyte Nuclear Factor 4 Hormones - metabolism Insulin Insulin - physiology Lipids. Glycolipids Liver Liver - metabolism Male Metabolisms and neurohumoral controls Mice Mice, Knockout Obesity - genetics Obesity - metabolism PGC-1 protein Phosphoenolpyruvate Carboxykinase (GTP) - genetics Phosphoenolpyruvate Carboxykinase (GTP) - metabolism Phosphoproteins - metabolism Rats Rats, Wistar Receptor, Insulin - genetics Receptor, Insulin - metabolism Receptors, Glucocorticoid - metabolism Response Elements RNA, Messenger - metabolism Rodents Tissues Transcription Factors - genetics Transcription Factors - metabolism Transcription Factors - physiology Tumor Cells, Cultured Vertebrates: anatomy and physiology, studies on body, several organs or systems |
| title | Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-11T19%3A37%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Control%20of%20hepatic%20gluconeogenesis%20through%20the%20transcriptional%20coactivator%20PGC-1&rft.jtitle=Nature%20(London)&rft.au=Spiegelman,%20Bruce%20M&rft.date=2001-09-13&rft.volume=413&rft.issue=6852&rft.spage=131&rft.epage=138&rft.pages=131-138&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/35093050&rft_dat=%3Cgale_proqu%3EA187967103%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=204483285&rft_id=info:pmid/11557972&rft_galeid=A187967103&rfr_iscdi=true |