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Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue in vitro.
Horm Metab Res 2003; 35(1):18-23HM

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-1beta (IL-1beta)-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-gamma agonists: troglitazone, pioglitazone, or ciglitazone) had any effects on PAI-1 production. Moreover, no effects on PAI-1 production were observed using various PPAR-alpha 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.

Authors+Show Affiliations

Department of Endocrinology and Metabolism C, Aarhus Amtssygehus, Aarhus University Hospital, Aarhus, Denmark.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12669266

Citation

He, G, et al. "Metformin, but Not Thiazolidinediones, Inhibits Plasminogen Activator Inhibitor-1 Production in Human Adipose Tissue in Vitro." Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme, vol. 35, no. 1, 2003, pp. 18-23.
He G, Pedersen SB, Bruun JM, et al. Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue in vitro. Horm Metab Res. 2003;35(1):18-23.
He, G., Pedersen, S. B., Bruun, J. M., Lihn, A. S., & Richelsen, B. (2003). Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue in vitro. Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme, 35(1), pp. 18-23.
He G, et al. Metformin, but Not Thiazolidinediones, Inhibits Plasminogen Activator Inhibitor-1 Production in Human Adipose Tissue in Vitro. Horm Metab Res. 2003;35(1):18-23. PubMed PMID: 12669266.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metformin, but not thiazolidinediones, inhibits plasminogen activator inhibitor-1 production in human adipose tissue in vitro. AU - He,G, AU - Pedersen,S B, AU - Bruun,J M, AU - Lihn,A S, AU - Richelsen,B, PY - 2003/4/2/pubmed PY - 2003/12/6/medline PY - 2003/4/2/entrez SP - 18 EP - 23 JF - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JO - Horm. Metab. Res. VL - 35 IS - 1 N2 - 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-1beta (IL-1beta)-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-gamma agonists: troglitazone, pioglitazone, or ciglitazone) had any effects on PAI-1 production. Moreover, no effects on PAI-1 production were observed using various PPAR-alpha 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. SN - 0018-5043 UR - https://www.unboundmedicine.com/medline/citation/12669266/Metformin_but_not_thiazolidinediones_inhibits_plasminogen_activator_inhibitor_1_production_in_human_adipose_tissue_in_vitro_ L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-2003-38386 DB - PRIME DP - Unbound Medicine ER -