Visit our Expo - Redox and Inflammation signaling 2012

Session XIV : Transcriptional and translational control Poster XIV, 64
The cAMP Responsive Unit of the human Insulin-like Growth Factor Binding Protein-1
(hIGFBP-1) gene promoter comprises a functional Insulin Response Element
Ghislaine Schweizer-Groyer 1, Guillaume Fallot 3, Françoise Cadepond 1 and André
Groyer 2
1 Inserm U.488, Lab hormones, 94276, Le Kremlin-Bicêtre Cédex, France ; 2 Inserm
U.683 and 3 Inserm U.481, Faculté de Médecine Xavier Bichat, 75870, Paris Cédex 18,
France. E-mail: groyer@bichat.inserm.fr
Insulin-like Growth Factor-Binding Protein-1 (IGFBP-1) is one of the genes involved in
glucose homeostasis. In vivo, its level is increased by glucocorticoids and glucagon (via
cAMP) and decreased by insulin, these variations being primarily correlated with IGFBP-1
gene transcription. A functional Insulin Response Element (IRE), localised immediately 5’ to
the Glucocorticoid Response Element (GRE), has already been shown to mediate insulin
inhibition of basal and glucocorticoid-induced stimulation of IGFBP-1 promoter activity.
In this work, using the human hepatoma HepG2 cells as a model system and transient
transfection, we showed : 1) that both basal and cAMP-induced hIGFBP-1 promoter (nt-1 to -
341) activity are inhibited by insulin; 2) that Forkhead Box class O (Foxo) transcription
factors enhance constitutive hIGFBP-1 promoter activity without interfering with stimulatory
effect of cAMP; 3) that PI-3’ kinase signaling is involved in the inhibition of both constitutive
and cAMP-induced promoter activity by insulin; 4) that the Foxos mediate the inhibitory
effect of insulin on transcription from the whole IGFBP-1 promoter; 5) that the cAMP
Responsive Unit (CRU) composed of a cAMP Responsive Element (CRE) and of a putative
IRE, is functional in mediating both cAMP stimulation and insulin inhibition of a
heterologous promoter and 6) that the inhibitory effects of insulin on the isolated CRU are
mediated by the Foxos.
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