title: Insulin stimulates IGFBP-2 expression in 3T3-L1 adipocytes through the PI3K/mTOR pathway.
abstract: Insulin-like growth factor binding protein 2 (IGFBP-2) has been implicated in the etiology of several diseases, including the metabolic syndrome. Although IGFBP-2 derives mostly from the liver, recent evidence in mice and humans indicate that aging and obesity are associated with altered IGFBP-2 levels in white adipocytes. The present study was aimed at determining the mechanisms that control IGFBP-2 expression in mature adipocytes. IGFBP-2 mRNA and protein expression in serum-deprived 3T3-L1 adipocytes were twofold increased by acute insulin treatment. Co-treatments with the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin or the mammalian target of rapamycin (mTOR) inhibitor rapamycin blunted the effects of insulin. Coherently, IGFBP-2 mRNA levels were robustly increased in adipocytes lacking either TSC2 or 4E-BP1. Insulin triggered the recruitment of CAAT/enhancer binding protein α (C/EBPα) to the IGFBP-2 proximal promoter. These findings suggest that insulin upregulates IGFBP-2 expression through a PI3K/mTOR/C/EBPα pathway in white adipocytes.
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Laval University, QC, Canada G1V 4G5.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Miard
authors.forename: Mathieu
authors.initials: M
authors.lastname: Laplante
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
authors.forename: Frédéric
authors.initials: F
authors.lastname: Picard
mesh_terms: D041721:3T3-L1 Cells; D048868:Adaptor Proteins, Signal Transducing; D052438:Adipocytes, White / Q000378:metabolism*; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D039642:Eukaryotic Initiation Factors; D007328:Insulin / Q000378:metabolism*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000172:deficiency; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000096:biosynthesis; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000172:deficiency; D000077191:Wortmannin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000730:Androstadienes; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D039642:Eukaryotic Initiation Factors; D007328:Insulin; D018971:Insulin-Like Growth Factor Binding Protein 2; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D012333:RNA, Messenger; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D000077191:Wortmannin; C499527:Eif4ebp1 protein, mouse; C000624653:TSC2 protein, human; C000624654:Tsc2 protein, mouse; C546843:mTOR protein, mouse