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l-Methionine Placental Uptake: Characterization and Modulation in Gestational Diabetes Mellitus

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Abstract

Our aim was to investigate the influence of gestational diabetes mellitus (GDM) and GDM-associated conditions upon the placental uptake of 14C-l-methionine (14C-l-Met). The 14C-l-Met uptake by human trophoblasts (TBs) obtained from normal pregnancies (normal trophoblast [NTB] cells) is mainly system l-type amino acid transporter 1 (LAT1 [L])-mediated, although a small contribution of system y+LAT2 is also present. Comparison of 14C-l-Met uptake by NTB and by human TBs obtained from GDM pregnancies (diabetic trophoblast [DTB] cells) reveals similar kinetics, but a contribution of systems A, LAT2, and b0+ and a greater contribution of system y+LAT1 appears to exist in DTB cells. Short-term exposure to insulin and long-term exposure to high glucose, tumor necrosis factor-α, and leptin decrease 14C-l-Met uptake in a human TB (Bewo) cell line. The effect of leptin was dependent upon phosphoinositide 3-kinase, extracellular-signal-regulated kinase 1/2 (ERK/MEK 1/2), and p38 mitogen-activated protein kinase. In conclusion, GDM does not quantitatively alter 14C-l-Met placental uptake, although it changes the nature of transporters involved in that process.

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Authors and Affiliations

  1. Department of Biochemistry (U38-FCT), Faculty of Medicine of Porto, University of Porto, Porto, 4200-319, Portugal

    João R. Araújo BSc, Ana Correia-Branco MSc, Pedro Gonçalves PhD, Elisa Keating PhD & Fátima Martel PhD

  2. Department of Obstetrics and Gynaecology, Centro Hospitalar S. João, Porto, Portugal

    Carla Ramalho PhD

  3. Department of Pharmacology and Therapeutics (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal

    Maria J. Pinho PhD

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  1. João R. Araújo BSc
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  2. Ana Correia-Branco MSc
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  3. Carla Ramalho PhD
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Correspondence to Fátima Martel PhD.

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Araújo, J.R., Correia-Branco, A., Ramalho, C. et al. l-Methionine Placental Uptake: Characterization and Modulation in Gestational Diabetes Mellitus. Reprod. Sci. 20, 1492–1507 (2013). https://doi.org/10.1177/1933719113488442

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