标题：Augmentation of synthesis of plasminogen activator inhibitor type 1 by insulin and insulin-like growth factor type I: implications for vascular disease in hyperinsulinemic states
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1991
卷号：88
期号：22
页码：9959-9963
DOI：10.1073/pnas.88.22.9959
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Accelerated atherosclerosis accompanying diabetes mellitus, obesity, and some types of hypertension has been associated with hyperinsulinemia, augmented plasma plasminogen activator inhibitor type 1 (PAI-1), or both. We hypothesized that insulin and insulin-like growth factor type I (IGF-I) can influence synthesis of PAI-1, thereby potentially attenuating fibrinolysis. In HepG2 cells used as a model system, concentrations of insulin and IGF-I consistent with those seen in plasma independently stimulated PAI-1 synthesis. Accumulation of PAI-1 protein in conditioned medium over 24 hr was stimulated more with insulin alone than with the combination. Synergistic increases were evident, however, in the accumulation of PAI-1 protein over 48 hr with a concomitant increase in PAI-1 mRNA. A 10- to 20-fold increase in IGF binding protein I mRNA was seen 16-48 hr after exposure of the HepG2 cells to insulin and IGF-I, an increase abolished by cycloheximide. The results obtained are consistent with the hypothesis that hyperinsulinemia coupled with physiologic concentrations of IGF-I may attenuate fibrinolytic activity in vivo, thereby contributing to accelerated atherosclerosis.
