Insulin induces REDD1 expression through hypoxia-inducible factor 1 activation in adipocytes.
REDD1 (regulated in development and DNA damage responses) is essential for the inhibition of mTORC1 (mammalian target of rapamycin complex) signaling pathway in response to hypoxia. REDD1 expression is regulated by many stresses such as hypoxia, oxidative stress, and energy depletion. However, the regulation of REDD1 expression in response to insulin remains unknown. In the present study, we demonstrate that in murine and in human adipocytes, insulin stimulates REDD1 expression. Insulin-induced REDD1 expression occurs through phosphoinositide 3-kinase/mTOR-dependent pathways. Moreover, using echinomycin, a hypoxia-inducible factor 1 (HIF-1) inhibitor, and HIF-1alpha small interfering RNA, we demonstrate that insulin stimulates REDD1 expression only through the transcription factor HIF-1. In conclusion, our study shows that insulin stimulates REDD1 expression in adipocytes.
Regazzetti
Claire
C
Mediterranean Research Centre for Molecular Medicine, Team Cellular and Molecular Physiopathology of Obesity and Diabetes, INSERM U 895, F-06204 Nice, France.
Bost
Frédéric
F
Le Marchand-Brustel
Yannick
Y
Tanti
Jean-François
JF
Giorgetti-Peraldi
Sophie
S
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004448:Echinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D004448:Echinomycin; D007004:Hypoglycemic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; C469991:DDIT4 protein, human; C469992:Ddit4 protein, mouse; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; C546842:MTOR protein, human; C546843:mTOR protein, mouse