Summary
Patients with non-insulin-dependent diabetes mellitus frequently have been associated
with elevation in plasma levels of PAI-1. Part of the variations in individual plasma
PAI-1 levels have been attributed to variations in the PAI-1 gene. In order to determine
whether insulin regulates PAI-1 expression in a genotype-specific manner, individual
human umbilical vein ECs (HUVECs) were genotyped using a HindIII RFLP and incubated in the absence/presence of insulin. Treatment of 1/1 PAI-1
genotype HUVECs with insulin increased secretion of PAI-1 antigen ~ 1.7 to 2.2-fold
and mRNA levels were increased ~ 1.8 to 2.8-fold. Treatment of HUVECs with actinomycin
D or puromycin completely abolished the induction of PAI-1 by insulin. The nuclear
run-on assays indicated ~3-4 fold increase in PAI-1 transcription rates. These in
vitro studies with the 1/1 PAI-1 genotyped cultured HUVECs, suggests that hyperinsulinemia
may be expected to increase EC PAI-1 synthesis in those patients with the responsive
1/1 genotype.
Key words
Endothelial cells - PAI-1 - insulin - genotypes - regulation