title: Selective insulin resistance in adipocytes.
abstract: Aside from glucose metabolism, insulin regulates a variety of pathways in peripheral tissues. Under insulin-resistant conditions, it is well known that insulin-stimulated glucose uptake is impaired, and many studies attribute this to a defect in Akt signaling. Here we make use of several insulin resistance models, including insulin-resistant 3T3-L1 adipocytes and fat explants prepared from high fat-fed C57BL/6J and ob/ob mice, to comprehensively distinguish defective from unaffected aspects of insulin signaling and its downstream consequences in adipocytes. Defective regulation of glucose uptake was observed in all models of insulin resistance, whereas other major actions of insulin such as protein synthesis and anti-lipolysis were normal. This defect corresponded to a reduction in the maximum response to insulin. The pattern of change observed for phosphorylation in the Akt pathway was inconsistent with a simple defect at the level of Akt. The only Akt substrate that showed consistently reduced phosphorylation was the RabGAP AS160 that regulates GLUT4 translocation. We conclude that insulin resistance in adipose tissue is highly selective for glucose metabolism and likely involves a defect in one of the components regulating GLUT4 translocation to the cell surface in response to insulin.
authors.affiliation: From the Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales 2010, Australia.
authors.forename: Shi-Xiong
authors.initials: SX
authors.lastname: Tan
authors.affiliation: From the Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales 2010, Australia.
authors.forename: Kelsey H
authors.initials: KH
authors.lastname: Fisher-Wellman
authors.affiliation: the Charles Perkins Centre, School of Molecular Biosciences and.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fazakerley
authors.affiliation: From the Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales 2010, Australia.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Ng
authors.affiliation: From the Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales 2010, Australia.
authors.forename: Himani
authors.initials: H
authors.lastname: Pant
authors.affiliation: From the Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales 2010, Australia.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: From the Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales 2010, Australia, the Charles Perkins Centre, School of Molecular Biosciences and.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Meoli
authors.affiliation: the School of Mathematics and Statistics, University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Adelle C F
authors.initials: AC
authors.lastname: Coster
authors.affiliation: the Charles Perkins Centre, School of Molecular Biosciences and jacqueline.stoeckli@sydney.edu.au.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Stöckli
authors.affiliation: the Charles Perkins Centre, School of Molecular Biosciences and the School of Medicine, University of Sydney, New South Wales 2006, Australia, and david.james@sydney.edu.au.
authors.forename: David E
authors.initials: DE
authors.lastname: James
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D059305:Diet, High-Fat / Q000009:adverse effects; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D051379:Mice; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
chemical_list: D007328:Insulin; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose
keywords: Adipocyte; Glucose Metabolism; Insulin; Insulin Action; Insulin Resistance; Lipolysis; Selective Insulin Resistance; White Adipose