Insulin Stimulates Tetrahydrobiopterin Synthesis in Mouse Brain Microvascular Endothelial Cells

Ishi, Masakazu; Shimizu, Shunichi; Nagai, Tsutomu; Kiuchi, Yuji; Yamamoto, Toshinori

doi:10.1515/pteridines.1999.10.4.213

Cited by 6 publications

(3 citation statements)

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“…In diabetic ß-cells, BH 4 content also seems to be decreased. We previously reported that insulin stimulates BH 4 synthesis in endothelial cells (18,19). In this study, the decrease in BH 4 content stimulated L-tyrosine-induced [Ca 2 ]¡ elevation.…”

Section: Discussionsupporting

confidence: 55%

Tetrahydrobiopterin Regulates L-tyrosine-induced Elevation of Cytosolic Calcium Concentration in Insulin-secreting Cells

et al. 2006

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Section: Discussionsupporting

confidence: 55%

Tetrahydrobiopterin Regulates L-tyrosine-induced Elevation of Cytosolic Calcium Concentration in Insulin-secreting Cells

et al. 2006

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“…Interestingly, Shinozaki et al (34) detected significant reduction of GTP cyclohydrolase I activity in aortas of insulin-resistant rats, suggesting that insulin may play an important role in control of tetrahydrobiopterin biosynthesis. Indeed, a study by Ishii et al (17) demonstrated that insulin stimulates biosynthesis of tetrahydrobiopterin in cultured mouse brain microvascular cells. The exact mechanism underlying the stimulatory effect of insulin remains to be determined.…”

Section: Effect Of Oxidative Stress On Tetrahydrobiopterin Metabolismmentioning

confidence: 99%

Vascular endothelial dysfunction: does tetrahydrobiopterin play a role?

Katušić

2001

American Journal of Physiology-Heart and Circulatory Physiology

239

176

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Tetrahydrobiopterin is one of the most potent naturally occurring reducing agents and an essential cofactor required for enzymatic activity of nitric oxide synthase (NOS). The exact role of tetrahydrobiopterin in the control of NOS catalytic activity is not completely understood. Existing evidence suggests that it can act as allosteric and redox cofactors. Suboptimal concentration of tetrahydrobiopterin reduces formation of nitric oxide and favors "uncoupling" of NOS leading to NOS-mediated reduction of oxygen and formation of superoxide anions and hydrogen peroxide. Recent findings suggest that accelerated catabolism of tetrahydrobiopterin in arteries exposed to oxidative stress may contribute to pathogenesis of endothelial dysfunction present in arteries exposed to hypertension, hypercholesterolemia, diabetes, smoking, and ischemia-reperfusion. Beneficial effects of acute and chronic tetrahydrobiopterin supplementation on endothelial function have been reported in experimental animals and humans. Furthermore, it appears that beneficial effects of some antioxidants (e.g., vitamin C) on vascular function could be mediated via increased intracellular concentration of tetrahydrobiopterin. In this review, the potential role of tetrahydrobiopterin in the pathogenesis of vascular endothelial dysfunction and mechanisms underlying beneficial vascular effects of tetrahydrobiopterin will be discussed.

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“…Biopterin was measured by reversed-phase high performance liquid cluomatography (HPLC) using fluorometric detection, as previously described (5) . Confluent endothelial cells in 6-well plates were washed three times with physiological saline solution (PSS , pH 7.4) containing 118.5 mM NaCl, 4 .74 mM KCI, 2.5 1Th1\;1 CaCl z , 1.18 mM MgS0 4 , 1.18 mM KH 2 P0 4 , 2.5 mM NaHC0 3 , 11 mM glucose and 10 mM N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid.…”

Section: Measurem Ent Ofbiopterinmentioning

confidence: 99%

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

et al. 2000

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We investigated the effects of troglitazone, which is a ligand of nuclear transcription factor peroxisome proliferator-activated receptor-y (PPAR-y), on insulin-Ll1duced 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 (10 )lg/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 ~lM). However, the expression of PPAR-y mRNA in untreated and insulin-treated endothelial cells was not detected. Moreover, bezafibrate (1-10 /lM), a ligand of PPAR-o, 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-y-and PPAR-o-independent mechanism.

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Insulin Stimulates Tetrahydrobiopterin Synthesis in Mouse Brain Microvascular Endothelial Cells

Cited by 6 publications

References 0 publications

Tetrahydrobiopterin Regulates L-tyrosine-induced Elevation of Cytosolic Calcium Concentration in Insulin-secreting Cells

Tetrahydrobiopterin Regulates L-tyrosine-induced Elevation of Cytosolic Calcium Concentration in Insulin-secreting Cells

Vascular endothelial dysfunction: does tetrahydrobiopterin play a role?

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

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