Up-regulated expression of plasminogen activator inhibitor-1 in Hep G2 cells: interrelationship between insulin and...

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)