Up-regulated expression of plasminogen activator inhibitor-1 in Hep G2 cells: interrelationship between insulin and insulin-like growth factor 1.
Insulin resistance represents a situation with a high risk of atherothrombosis and is accompanied by increased plasma plasminogen activator inhibitor-1 (PAI-1) levels. Fasting insulin level is highly correlated with PAI-1 levels in plasma. It has been shown that insulin increases PAI-1 synthesis by the human hepatoma cell line Hep G2. Moreover when Hep G2 cells expressing a down-regulation of insulin receptors by incubation with 10(-7) M insulin, were stimulated by 10(-9) M insulin, an overexpression of PAI-1 synthesis was observed despite a reduced number of insulin receptors. Insulin-like growth factor 1 (IGF-1) shares many properties with insulin. The aim of the present study was to evaluate the effect of IGF-1 on PAI-1 synthesis by Hep G2 cells down-regulated either by insulin or IGF-1. Incubation of Hep G2 cells with increasing doses from 10(-9) to 10(-7) M IGF-1 induced a dose-dependent stimulation of PAI-1 synthesis up to 4.5-fold the control level. When cells were first pre-incubated with 10(-7) M IGF-1 for 18 h, acid washed, and then stimulated with 10(-9) M IGF-1, the expression of IGF-1 receptors was greatly reduced (up to 70%). In contrast PAI-1 secretion was increased 3.4-fold the level of control cells and by 1.9-fold the level of cells first stimulated with 10(-9) M IGF-1. Both transcripts of PAI-1 mRNA were also increased.(ABSTRACT TRUNCATED AT 250 WORDS)
Anfosso
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Laboratoire d'Hématologie, INSERM CJF 93/12, Faculté de Médecine, Marseille, France.
Alessi
M C
MC
Nalbone
G
G
Chomiki
N
N
Henry
M
M
Juhan-Vague
I
I
D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D017526:Receptor, IGF Type 1 / Q000187:drug effects; D011972:Receptor, Insulin / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin