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.
Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3-L1 Cells
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Adaptor Proteins, Signal Transducing
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Adipocytes, White / metabolism*
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Androstadienes / pharmacology
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Animals
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CCAAT-Enhancer-Binding Proteins / metabolism
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Carrier Proteins
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Cell Cycle Proteins
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Cell Line
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Eukaryotic Initiation Factors
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Insulin / metabolism*
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Insulin-Like Growth Factor Binding Protein 2 / biosynthesis*
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Insulin-Like Growth Factor Binding Protein 2 / genetics
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Mice
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphoproteins / deficiency
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Promoter Regions, Genetic
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RNA, Messenger / biosynthesis
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Sirolimus / pharmacology
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TOR Serine-Threonine Kinases / metabolism*
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins / deficiency
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Wortmannin
Substances
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Adaptor Proteins, Signal Transducing
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Androstadienes
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CCAAT-Enhancer-Binding Proteins
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Carrier Proteins
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Cell Cycle Proteins
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Eif4ebp1 protein, mouse
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Eukaryotic Initiation Factors
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Insulin
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Insulin-Like Growth Factor Binding Protein 2
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Phosphoproteins
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RNA, Messenger
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TSC2 protein, human
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Tsc2 protein, mouse
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Tuberous Sclerosis Complex 2 Protein
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Tumor Suppressor Proteins
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mTOR protein, mouse
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TOR Serine-Threonine Kinases
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Sirolimus
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Wortmannin