The Effects of Insulin-Like Growth Factor-1 on Plasminogen Activator Inhibitor-1 Synthesis and Secretion: Results from In Vitro and In Vivo Studies

S J Padayatty; S Orme; P D Zenobi; M H Stickland; P E Belchetz; P J Grant

doi:10.1055/s-0038-1649716

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 1993; 70(06): 1009-1013
DOI: 10.1055/s-0038-1649716

Original Article

Fibrinolysis

Schattauer GmbH Stuttgart

The Effects of Insulin-Like Growth Factor-1 on Plasminogen Activator Inhibitor-1 Synthesis and Secretion: Results from In Vitro and In Vivo Studies

Authors

S J Padayatty

¹The Department of Endocrinology, The General Infirmary at Leeds, UK
S Orme

¹The Department of Endocrinology, The General Infirmary at Leeds, UK
P D Zenobi

²The Division of Endocrinology, Department of Internal Medicine, University Hospital, Zurich, Switzerland
M H Stickland

The Academic Unit of Medicine, The General Infirmary at Leeds, UK
P E Belchetz

¹The Department of Endocrinology, The General Infirmary at Leeds, UK
P J Grant

The Academic Unit of Medicine, The General Infirmary at Leeds, UK

Abstract

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Summary

In vitro studies have shown that insulin and IGF-1 releases the fibrinolytic inhibitor plasminogen activator inhibitor-1 (PAI-1) from cells of hepatic origin. To investigate the effects of IGF-1 on fibrinolysis: 1) cultured hepatoma cells were grown in the presence of IGF-1 and media collected for secreted PAI-1 and cells probed for PAI-1 mRNA, 2) 8 hypopituitary patients were treated with recombinant human growth hormone (rhGH) and 3) 5 type 2 diabetic patients were treated with recombinant human IGF-1 (rhIGF-1). Treatment of Hep G2 cells with IGF-1 (1000 ng/ml) increased secretion of PAI-1 from a median value of 80 ng/10⁶ cells (range 21-91) to 144 ng/10⁶ cells (range 128-169) after 24 h (p <0.01). Synthesis of PAI-1 mRNA increased in a similar fashion. Treatment of hypopituitary patients with rhGH led to an increase in circulating IGF-1 from a mean value of 166 (range 41-324) ng/ml at baseline to 322 (77-575) ng/ml at 4 weeks and 259 (104-533) ng/ml after 8 weeks (p <0.02). Despite this, no changes in circulating PAI-1 or fibrinolysis occurred. Type II diabetic patients treated with rhIGF-1 showed an increase in circulating IGF-1 from a mean value of 120 ng/ml (range 109-196), at baseline to 823 ng/ml (585-894) after 5 days. This also was not associated with changes in circulating PAI-1 or in fibrinolysis. The results confirm that IGF-1 induces the synthesis of PAI-1 in Hep G2 cells. However, marked increases in IGF-1 had no effect on circulating PAI-1 or fibrinolysis.

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Referenzen

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