Insulin stimulates the synthesis of plasminogen activator inhibitor 1 by the human hepatocellular cell line Hep G2.
Secretion of plasminogen activator inhibitor 1 (PAI-1) by cultures of human umbilical vein endothelial cells and human hepatocellular cell line Hep G2 was evaluated after insulin stimulation. The secretion of PAI-1 antigen and activity was measured in the conditioned medium and the cellular extracts after incubation of confluent cultures with 1% serum medium for 24 hours. Insulin induced a dose dependent increase of the PAI-1 secretion by Hep G2 cell line. At 10(-8) M a two fold increase of PAI-1 antigen and activity were observed whereas alpha 2 antiplasmin and fibrinogen were not significantly modified. No effect of insulin was observed on PAI-1 antigen and PAI activity production by human endothelial cells whereas endotoxin resulted in a two fold increase in PAI-1 secretion. In recent clinical studies we have demonstrated that the level of plasma insulin correlated with that of PAI-1. Thus we hypothesize that hepatocytes represent a physiological source of plasma PAI-1 which is modulated by plasma insulin level.
Alessi
M C
MC
Laboratory of Hematology, CHU Timone, Marseille, France.
Juhan-Vague
I
I
Kooistra
T
T
Declerck
P J
PJ
Collen
D
D
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005340:Fibrinogen / Q000096:biosynthesis; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000096:biosynthesis
D006023:Glycoproteins; D007328:Insulin; D015849:Plasminogen Inactivators; D000979:alpha-2-Antiplasmin; D003609:Dactinomycin; D005340:Fibrinogen; D003513:Cycloheximide; D010960:Plasminogen Activators