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: Zhuo Li, Stéphanie Miard, Mathieu Laplante, Nahum Sonenberg, Frédéric Picard
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 358 Issue 1 Pg. 63-8 (Jul 06 2012) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 22410287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Adaptor Proteins, Signal Transducing
• Androstadienes
• CCAAT-Enhancer-Binding Proteins
• Carrier Proteins
• Cell Cycle Proteins
• Eif4ebp1 protein, mouse
• Eukaryotic Initiation Factors
• Insulin
• Insulin-Like Growth Factor Binding Protein 2
• Phosphoproteins
• RNA, Messenger
• TSC2 protein, human
• Tsc2 protein, mouse
• Tuberous Sclerosis Complex 2 Protein
• Tumor Suppressor Proteins
• mTOR protein, mouse
• TOR Serine-Threonine Kinases
• Sirolimus
• Wortmannin

Topics

• 3T3-L1 Cells
• Adaptor Proteins, Signal Transducing
• Adipocytes, White (metabolism)
• Androstadienes (pharmacology)
• Animals
• CCAAT-Enhancer-Binding Proteins (metabolism)
• Carrier Proteins
• Cell Cycle Proteins
• Cell Line
• Eukaryotic Initiation Factors
• Insulin (metabolism)
• Insulin-Like Growth Factor Binding Protein 2 (biosynthesis, genetics)
• Mice
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphoproteins (deficiency)
• Promoter Regions, Genetic
• RNA, Messenger (biosynthesis)
• Sirolimus (pharmacology)
• TOR Serine-Threonine Kinases (metabolism)
• Tuberous Sclerosis Complex 2 Protein
• Tumor Suppressor Proteins (deficiency)
• Wortmannin