1Department of Biochemistry (U38-FCT), Faculty of Medicine, University of Porto, Porto, Portugal.
Reprod Sci. 2013 Dec;20(12):1492-507. doi: 10.1177/1933719113488442. Epub 2013 May 7.
Our aim was to investigate the influence of gestational diabetes mellitus (GDM) and GDM-associated conditions upon the placental uptake of (14)C-l-methionine ((14)C-l-Met). The (14)C-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 (14)C-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 b(0+) 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 (14)C-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 (14)C-l-Met placental uptake, although it changes the nature of transporters involved in that process.
我们的目的是研究妊娠糖尿病（GDM）和 GDM 相关病症对（14）C-蛋氨酸（（14）C-l-Met）胎盘摄取的影响。正常妊娠（正常滋养层[NTB]细胞）中获得的人滋养层（TBs）对（14）C-l-Met 的摄取主要是通过系统 l 型氨基酸转运体 1（LAT1 [L]）介导的，尽管系统 y(+)LAT2 也有少量贡献。与 NTB 相比，来自 GDM 妊娠（糖尿病滋养层[DTB]细胞）的人 TBs 对（14）C-l-Met 的摄取揭示了相似的动力学，但系统 A、LAT2、b(0+)的贡献更大，系统 y(+)LAT1 的贡献更大，似乎存在于 DTB 细胞中。胰岛素的短期暴露和高葡萄糖、肿瘤坏死因子-α和瘦素的长期暴露会降低人 TB（Bewo）细胞系中（14）C-l-Met 的摄取。瘦素的作用依赖于磷酸肌醇 3-激酶、细胞外信号调节激酶 1/2（ERK/MEK 1/2）和 p38 丝裂原活化蛋白激酶。总之，GDM 不会定量改变（14）C-l-Met 胎盘摄取，尽管它改变了参与该过程的转运体的性质。
