{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:07:03Z","timestamp":1791245223837,"version":"4.1.0"},"reference-count":32,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,3,27]]},"abstract":"<jats:p>Recent data indicate that sustained elevations in plasma insulin\n suppress the mRNA for IRS-2, a component of the insulin signaling\n pathway in liver, and that this deficiency contributes to hepatic\n insulin resistance and inappropriate gluconeogenesis. Here, we use\n nuclear run-on assays to show that insulin inhibits transcription of\n the IRS-2 gene in the livers of intact rats. Insulin also inhibited\n transcription of a reporter gene driven by the human IRS-2 promoter\n that was transfected into freshly isolated rat hepatocytes. The human\n promoter contains a heptanucleotide sequence, TGTTTTG, that is\n identical to the insulin response element (IRE) identified previously\n in the promoters of insulin-repressed genes. Single base pair\n substitutions in this IRE decreased transcription of the IRS-2-driven\n reporter in the absence of insulin and abolished insulin-mediated\n repression. We conclude that insulin represses transcription of the\n IRS-2 gene by blocking the action of a positive factor that binds to\n the IRE. Sustained repression of IRS-2, as occurs in chronic\n hyperinsulinemia, contributes to hepatic insulin resistance and\n accelerates the development of the diabetic state.<\/jats:p>","DOI":"10.1073\/pnas.071054598","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"3756-3761","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":91,"title":["Insulin inhibits transcription of IRS-2 gene in rat liver through an insulin response element (IRE) that resembles IREs of other insulin-repressed genes"],"prefix":"10.1073","volume":"98","author":[{"given":"Jiandi","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, University of Texas Southwestern\r Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiafu","family":"Ou","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Texas Southwestern\r Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuriy","family":"Bashmakov","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Texas Southwestern\r Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay D.","family":"Horton","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Texas Southwestern\r Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Texas Southwestern\r Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L.","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, University of Texas Southwestern\r Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,3,20]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.43.8.1066"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(05)00010-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006806722619"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/36116"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006490200"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb01045.x"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/43448"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1996.76.4.1109"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M004898200"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1515\/JBCPP.1999.10.2.119"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.24.16741"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.24.17184"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.10.7289"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(83)98152-1"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.23577"},{"key":"e_1_3_3_16_2","volume-title":"Molecular Cloning: A Laboratory Manual","author":"Sambrook J","year":"2001","unstructured":"J Sambrook, D W Russell Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Lab. 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