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Horm Metab Res 2003; 35(1): 18-23
DOI: 10.1055/s-2003-38386
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Metformin, but not Thiazolidinediones, Inhibits Plasminogen Activator Inhibitor-1 Production in Human Adipose Tissue in Vitro

G.  He1 , S.  B.  Pedersen1 , J.  M.  Bruun1 , A.  S.  Lihn1 , B.  Richelsen1
  • 1Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, Aarhus, Denmark
Further Information

Publication History

Received 14 February 2002

Accepted after revision 8 July 2002

Publication Date:
01 April 2003 (online)

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Abstract

Biguanides and thiazolidinediones (TZDs), which are primarily used as anti-diabetic drugs, are also associated with other beneficial effects on cardiovascular risk factors such as reduced plasma plasminogen activator inhibitor-1 (PAI-1) concentration in both diabetic and non-diabetic obese subjects. Since human adipose tissue is of importance for the production of PAI-1, the aim of the present study was to investigate the possible direct effects of these anti-diabetic agents on PAI-1 mRNA and secretion by human adipose tissue. Adipose tissue was obtained from biopsies taken from the subcutaneous abdominal depot. Adipose tissue fragments, isolated mature adipocytes, and preadipocytes were incubated in vitro with metformin and various TZDs. Metformin (0.1 - 10 mM) dose-dependently decreased PAI-1 production (and PAI-1 mRNA) under both basal (43 % inhibition at 10 mM, p < 0.05) and interleukin-1β (IL-1β)-stimulated conditions where the levels were inhibited by 47.8 % at 1 mM metformin (p < 0.05) and by 100 % at 10 mM (p < 0.01). None of the TZDs tested (PPAR-γ agonists: troglitazone, pioglitazone, or ciglitazone) had any effects on PAI-1 production. Moreover, no effects on PAI-1 production were observed using various PPAR-α agonists such as 5, 8, 11, 14-eicosatetraynoic acid (ETYA), Wy14643 and fenofibrate. Our findings indicate no direct effects of TZDs on PAI-1 secretion, whereas metformin was able to directly inhibit PAI-1 production in human adipose tissue.

Key words

Plasminogen Activator Inhibitor-1 - Human Adipose Tissue - Metformin - Thiazolidinediones - Gene Expression - Obesity

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Dr. B. Richelsen

Department of Endocrinology and Metabolism · Aarhus Amtssygehus, Aarhus University Hospital

Tage Hansensgade 2 · 8000 Aarhus C. · Denmark ·

Phone: + 45 (89) 497 679

Fax: + 45 (89) 497 659

Email: br@aas.auh.dk