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However, adipose conversion was inhibited by indinavir (by 50\u201360%), as shown by 1) the decrease in the number of newly formed adipocytes; 2) the lower level of the adipogenic protein markers, sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator\u2013activated receptor-\u03b3 (PPAR-\u03b3), and the insulin receptor (IR); and 3) the lack of SREBP-1 and PPAR-\u03b3 immunoreactivity in the nucleus of most indinavir-treated cells. Partial adipose conversion also correlated with an accumulation of SREBP-1 at the nuclear periphery and an alteration in its electrophoretic mobility. Defective expression and nuclear localization of PPAR-\u03b3 probably resulted from the decreased level of nuclear SREBP-1. Indinavir also rendered 3T3-F442A adipocytes resistant to insulin for mitogen-activated protein kinase activation at a step distal to IR substrate-1 tyrosine phosphorylation. Hence, indinavir impairs differentiation at an early step of adipose conversion probably involving the process controlling SREBP-1 intranuclear localization.<\/jats:p>","DOI":"10.2337\/diabetes.50.6.1378","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"1378-1388","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":254,"title":["The HIV Protease Inhibitor Indinavir Impairs Sterol Regulatory Element-Binding Protein-1 Intranuclear Localization, Inhibits Preadipocyte Differentiation, and Induces Insulin Resistance"],"prefix":"10.2337","volume":"50","author":[{"given":"Martine","family":"Caron","sequence":"first","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U 402, Faculte\u0301 de Me\u0301decine Saint-Antoine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Auclair","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U 402, Faculte\u0301 de Me\u0301decine Saint-Antoine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Vigouroux","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U 402, Faculte\u0301 de Me\u0301decine Saint-Antoine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Glorian","sequence":"additional","affiliation":[{"name":"INSERM U 530, Centre Universitaire des Saints Pe\u0300res, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Forest","sequence":"additional","affiliation":[{"name":"INSERM U 530, Centre Universitaire des Saints Pe\u0300res, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Capeau","sequence":"additional","affiliation":[{"name":"Institut National de la Sante\u0301 et de la Recherche Me\u0301dicale (INSERM) U 402, Faculte\u0301 de Me\u0301decine Saint-Antoine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031207111088700_R1","doi-asserted-by":"crossref","unstructured":"Carr A, Samaras K, Burton S: A syndrome of peripheral lipodystrophy, hyperlipidemia and insulin resistance in patients receiving HIV protease inhibitors. 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