{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T06:19:26Z","timestamp":1772691566559,"version":"3.50.1"},"reference-count":35,"publisher":"Proceedings of the National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2003,6,24]]},"abstract":"<jats:p>\n            Glucose homeostasis is controlled by insulin in part through the  translocation of intracellular glucose transporter 4 to the plasma membrane in  muscle and fat cells. Akt\/protein kinase B downstream of phosphatidylinositol  3-kinase has been implicated in this insulin-signaling pathway, but results  with a variety of reagents including  Akt1\n            <jats:sup>\u2013<\/jats:sup>\n            <jats:sup>\/<\/jats:sup>\n            <jats:sup>\u2013<\/jats:sup>\n            and  Akt2\n            <jats:sup>\u2013<\/jats:sup>\n            <jats:sup>\/<\/jats:sup>\n            <jats:sup>\u2013<\/jats:sup>\n            mice have been equivocal.  Here we report the application of small interfering RNA-directed gene  silencing to deplete both Akt1 and Akt2 in cultured 3T3-L1 adipocytes. Loss of  Akt1 alone slightly impaired insulin-mediated hexose transport activity but  had no detectable effect on glycogen synthase kinase (GSK)-3 phosphorylation.  In contrast, depletion of Akt2 alone by 70% inhibited approximately half of  the insulin responsiveness. Combined depletions of Akt1 plus Akt2 in these  cells even more markedly attenuated insulin action on glucose transporter 4  movements, hexose transport activity, and GSK-3 phosphorylation. These data  demonstrate a primary role of Akt2 in insulin signaling, significant  functional redundancy of Akt1 and Akt2 isoforms in this pathway, and an  absolute requirement of Akt protein kinases for regulation of glucose  transport and GSK-3 in cultured adipocytes.\n          <\/jats:p>","DOI":"10.1073\/pnas.1332633100","type":"journal-article","created":{"date-parts":[[2003,6,24]],"date-time":"2003-06-24T17:47:39Z","timestamp":1056476859000},"page":"7569-7574","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":305,"title":["Insulin signaling through Akt\/protein kinase B analyzed by small  interfering RNA-mediated gene silencing"],"prefix":"10.1073","volume":"100","author":[{"given":"Zhen Y.","family":"Jiang","sequence":"first","affiliation":[{"name":"Program in Molecular Medicine, University of  Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605; and  Dharmacon Research, Inc., 1376 Miners Drive,  Lafayette, CO 80026"}]},{"given":"Qiong L.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of  Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605; and  Dharmacon Research, Inc., 1376 Miners Drive,  Lafayette, CO 80026"}]},{"given":"Kerri A.","family":"Coleman","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of  Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605; and  Dharmacon Research, Inc., 1376 Miners Drive,  Lafayette, CO 80026"}]},{"given":"My","family":"Chouinard","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of  Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605; and  Dharmacon Research, Inc., 1376 Miners Drive,  Lafayette, CO 80026"}]},{"given":"Queta","family":"Boese","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of  Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605; and  Dharmacon Research, Inc., 1376 Miners Drive,  Lafayette, CO 80026"}]},{"given":"Michael P.","family":"Czech","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, University of  Massachusetts Medical School, 373 Plantation Street, Worcester, MA 01605; and  Dharmacon Research, Inc., 1376 Miners Drive,  Lafayette, CO 80026"}]}],"member":"341","published-online":{"date-parts":[[2003,6,13]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm782"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)85561-8"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI6609"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00514.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.4.1865"},{"key":"e_1_3_2_6_2","first-page":"31372","volume":"49","year":"1996","unstructured":"Kohn, A. 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