caa a22 4500 475771834 CHVBK 20180406123619.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/s001250050057 doi (NATIONALLICENCE)springer-10.1007/s001250050057 Troglitazone reduces plasminogen activator inhibitor-1 expression and secretion in cultured human adipocytes [Elektronische Daten] [H. Gottschling-Zeller, K. Röhrig, H. Hauner] Abstract : Aims/hypothesis. Increased plasma plasminogen activator inhibitor-1 (PAI-1) concentrations are characteristic for subjects with insulin resistance and could contribute to the increased cardiovascular risk in this state. In this study, we investigated the effect of troglitazone, a ligand of the nuclear receptor peroxisome proliferator activated receptor-γ, on PAI-1 expression and secretion in human adipocytes.¶Methods. We used two models: in vitro differentiated subcutaneous and omental adipocytes cultured under serum-free conditions and isolated subcutaneous and omental fat cells kept in suspension culture. Plasminogen activator inhibitor-1 protein was measured by ELISA, PAI-1 mRNA by a semiquantitative RT-PCR technique.¶Results. Exposure of in vitro differentiated subcutaneous adipocytes from young normal-weight females to 1 μg/ml troglitazone for 72 h caused a reduction of both PAI-1 secretion (by 29 ± 5 %; p < 0.01) and PAI-1 mRNA expression (by 26 ± 3 %; p < 0.05). In cultures from severely obese subjects, troglitazone induced a decrease of PAI-1 antigen secretion from newly differentiated omental adipocytes by 49 ± 8 % (p < 0.01) and from subcutaneous adipocytes by 30 ± 7 % (p < 0.05). Exposure of freshly isolated subcutaneous and omental adipocytes in suspension culture to troglitazone induced a similar reduction of PAI-1 concentration in the culture medium (by 35 ± 11 %, p < 0.05. and 33 ± 8 %, p < 0.05 compared with control, respectively).¶Conclusion/interpretation. This study provides evidence that troglitazone reduces PAI-1 production in human adipocytes, probably at the transcriptional level. This observation could point to a new beneficial effect of troglitazone, particularly in obese subjects, which could be associated with a reduced cardiovascular risk. [Diabetologia (2000) 43: 377-383] Springer-Verlag Berlin Heidelberg, 2000 Keywords Plasminogen activator inhibitor-1, troglitazone, human adipocytes, Type II diabetes, obesity nationallicence Gottschling-Zeller H. Diabetes Research Institute at the Heinrich-Heine-University Düsseldorf, Clinical Department, Düsseldorf, Germany, DE aut Röhrig K. Diabetes Research Institute at the Heinrich-Heine-University Düsseldorf, Clinical Department, Düsseldorf, Germany, DE aut Hauner H. Diabetes Research Institute at the Heinrich-Heine-University Düsseldorf, Clinical Department, Düsseldorf, Germany, DE aut https://doi.org/10.1007/s001250050057 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250050057 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gottschling-Zeller H. Diabetes Research Institute at the Heinrich-Heine-University Düsseldorf, Clinical Department, Düsseldorf, Germany, DE aut NATIONALLICENCE 700 1- Röhrig K. Diabetes Research Institute at the Heinrich-Heine-University Düsseldorf, Clinical Department, Düsseldorf, Germany, DE aut NATIONALLICENCE 700 1- Hauner H. Diabetes Research Institute at the Heinrich-Heine-University Düsseldorf, Clinical Department, Düsseldorf, Germany, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer