{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:31:24Z","timestamp":1791048684683,"version":"4.1.0"},"reference-count":21,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5906","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Science"],"published-print":{"date-parts":[[2008,11,28]]},"abstract":"<jats:p>\n                    Hepatic glucose production is critical for basal brain function and survival when dietary glucose is unavailable. Glucose-6-phosphatase (G6Pase) is an essential, rate-limiting enzyme that serves as a terminal gatekeeper for hepatic glucose release into the plasma. Mutations in\n                    <jats:italic>G6Pase<\/jats:italic>\n                    result in Von Gierke's disease (glycogen storage disease\u20131a), a potentially fatal genetic disorder. We have identified the transcriptional coactivator SRC-2 as a regulator of fasting hepatic glucose release, a function that SRC-2 performs by controlling the expression of hepatic\n                    <jats:italic>G6Pase<\/jats:italic>\n                    . SRC-2 modulates\n                    <jats:italic>G6Pase<\/jats:italic>\n                    expression directly by acting as a coactivator with the orphan nuclear receptor ROR\u03b1. In addition, SRC-2 ablation, in both a whole-body and liver-specific manner, resulted in a Von Gierke's disease phenotype in mice. Our results position SRC-2 as a critical regulator of mammalian glucose production.\n                  <\/jats:p>","DOI":"10.1126\/science.1164847","type":"journal-article","created":{"date-parts":[[2008,11,27]],"date-time":"2008-11-27T17:36:45Z","timestamp":1227807405000},"page":"1395-1399","source":"Crossref","is-referenced-by-count":149,"title":["Absence of the SRC-2 Coactivator Results in a Glycogenopathy Resembling Von Gierke's Disease"],"prefix":"10.1126","volume":"322","author":[{"given":"Atul R.","family":"Chopra","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Francois","family":"Louet","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pradip","family":"Saha","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"An","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"DeMayo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"York","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saul","family":"Karpen","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Finegold","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher B.","family":"Newgard","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bert W.","family":"O'Malley","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA."},{"name":"Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Department of Pathology, Baylor College of Medicine, Houston, TX 77030, USA."},{"name":"Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC27710, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.19.1.379"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3620513"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1996.0341"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-152808-9.50009-2"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(79)90447-8"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0696-203"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-0122"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01169-8"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00654-06"},{"key":"e_1_3_2_11_2","first-page":"e011","volume":"5","year":"2007","unstructured":"A. Mukherjee, P. Amato, D. C. Allred, F. J. DeMayo, J. P. Lydon, Nucl. Recept. Signal.5, e011 (2007).","journal-title":"Nucl. Recept. Signal."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10024-001-0139-6"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.16.5923-5937.2002"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-4242"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2004.23.592"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.30.21285"},{"key":"e_1_3_2_17_2","first-page":"1550","volume":"13","year":"1999","unstructured":"G. B. Atkinset al., Mol. Endocrinol.13, 1550 (1999).","journal-title":"Mol. Endocrinol."},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/35093050"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.01.025"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.024"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300188"},{"key":"e_1_3_2_22_2","unstructured":"We thank O. McGuinness for help with assessment of liver glycogen and triglyceride content; D. White for help with primary hepatocyte isolation; S. Zhou and J. Song for help with animal breeding; J. Barish for performing the electron microscopy; J. Lin for the ROR\u03b1 adenovirus; J. Lydon for the SRC-2 F\/F mice and M. Stallcup for the SRC-2 activation domain mutants; R. Lanz for help with QPCR setup and analysis; M. Muehlbauer for help with plasma analysis of various metabolites; H. Klein and S. Greene for help with figure and model construction; and J. Sagen and C. Foulds for helpful discussion and critical reading of the manuscript. F.D. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grant PO1 DK59820). L.C. is supported by the NIH (grant HL51586). J.X. is supported by the NIH (DK58242). C.B.N. is supported by the NIH (grant PO1 DK58398). B.W.O. is supported by the NIDDK (grant PO1 DK59820) Nuclear Receptor Signaling Atlas (NURSA) (U19 DK062434) and a grant from the Welch Foundation."}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.1164847","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T04:22:09Z","timestamp":1704860529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.1164847"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,11,28]]},"references-count":21,"journal-issue":{"issue":"5906","published-print":{"date-parts":[[2008,11,28]]}},"alternative-id":["10.1126\/science.1164847"],"URL":"https:\/\/doi.org\/10.1126\/science.1164847","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1135857.619842","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1135857.592943","asserted-by":"object"}]},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,11,28]]}}}