Troglitazone Stimulates the Insulin-induced Tetrahydrobiopterin Synthesis In Vascular Endothelial Cells

We investigated the effects of troglitazone, which is a ligand of nuclear transcription factor peroxisome proliferator- activated receptor-γ (PPAR-γ), on insulin-induced tetrahydrobiopterin (BH4) synthesis in mouse brain microvascular endothelial cells (MBMECs). BH4 content was determined as biopterin, by reversed-phase high performance liquid chromatography using fluorometric detection. Measurement of mRNA level of GTP cyclohydrolase I (GTPCH), which is a rate-limiting enzyme for de novo BH4 synthesis, was performed by reverse transcription- polymerase chain reaction (RT -PCR). Addition of insulin (10µg/ml) to endothelial cells increased intracellular BH4 content and GTPCH mRNA level, and the insulin-induced increase in BH4 content and GTPCH mRNA level was further stimulated by co-treatment with troglitazone (0.3-3 µM). However, the expression of PPAR-γ mRNA in untreated and insulin-treated endothelial cells was not detected. Moreover, bezafibrate (1-10 µM), a ligand of PPAR-δ, did not affect BH4 synthesis in insulin-treated endothehal cells. These findings suggest that troglitazone stimulates insulin-induced BH4 synthesis in endothelial cells with the induction of GTPCH through PPAR-γ- and PPAR-δ-independent mechanism

Abstract licence: CC BY

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