{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T15:11:28Z","timestamp":1788275488008,"version":"build-2803163510"},"reference-count":39,"publisher":"Portland Press Ltd.","issue":"2","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":2414,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,1,15]]},"abstract":"<jats:p>AS160 (Akt substrate of 160\u00a0kDa) is a Rab GTPase-activating protein implicated in insulin control of GLUT4 (glucose transporter 4) trafficking. In humans, a truncation mutation (R363X) in one allele of AS160 decreased the expression of the protein and caused severe postprandial hyperinsulinaemia during puberty. To complement the limited studies possible in humans, we generated an AS160-knockout mouse. In wild-type mice, AS160 expression is relatively high in adipose tissue and soleus muscle, low in EDL (extensor digitorum longus) muscle and detectable in liver only after enrichment. Despite having lower blood glucose levels under both fasted and random-fed conditions, the AS160-knockout mice exhibited insulin resistance in both muscle and liver in a euglycaemic clamp study. Consistent with this paradoxical phenotype, basal glucose uptake was higher in AS160-knockout primary adipocytes and normal in isolated soleus muscle, but their insulin-stimulated glucose uptake and overall GLUT4 levels were markedly decreased. In contrast, insulin-stimulated glucose uptake and GLUT4 levels were normal in EDL muscle. The liver also contributes to the AS160-knockout phenotype via hepatic insulin resistance, elevated hepatic expression of phosphoenolpyruvate carboxykinase isoforms and pyruvate intolerance, which are indicative of increased gluconeogenesis. Overall, as well as its catalytic function, AS160 influences expression of other proteins, and its loss deregulates basal and insulin-regulated glucose homoeostasis, not only in tissues that normally express AS160, but also by influencing liver function.<\/jats:p>","DOI":"10.1042\/bj20120702","type":"journal-article","created":{"date-parts":[[2012,10,22]],"date-time":"2012-10-22T08:34:06Z","timestamp":1350894846000},"page":"479-489","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["AS160 deficiency causes whole-body insulin resistance via composite effects in multiple tissues"],"prefix":"10.1042","volume":"449","author":[{"given":"Hong\u00a0Yu","family":"Wang","sequence":"first","affiliation":[{"name":"MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serge","family":"Ducommun","sequence":"additional","affiliation":[{"name":"MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, U.K."},{"name":"Nestl\u00e9 Institute of Health Sciences SA, Campus EPFL, Quartier de l'Innovation, B\u00e2timent G, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Quan","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingxian","family":"Xie","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u00a0H.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology and Biophysics, Vanderbilt University, School of Medicine, 2200 Pierce Ave, Nashville, TN 37232, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, U.K."},{"name":"Nestl\u00e9 Institute of Health Sciences SA, Campus EPFL, Quartier de l'Innovation, B\u00e2timent G, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Mackintosh","sequence":"additional","affiliation":[{"name":"MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, U.K."},{"name":"Division of Cell and Developmental Biology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Chen","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Pukou District, Nanjing 210061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2012,12,14]]},"reference":[{"key":"2021112215542665200_B1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/333183a0","article-title":"Insulin-regulatable tissues express a unique insulin-sensitive glucose transport protein","volume":"333","author":"James","year":"1988","journal-title":"Nature"},{"key":"2021112215542665200_B2","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cmet.2007.03.006","article-title":"The GLUT4 glucose transporter","volume":"5","author":"Huang","year":"2007","journal-title":"Cell Metab."},{"key":"2021112215542665200_B3","doi-asserted-by":"crossref","first-page":"14599","DOI":"10.1074\/jbc.C300063200","article-title":"Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation","volume":"278","author":"Sano","year":"2003","journal-title":"J. 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