Ruiz-Palacios Maria, Prieto-Sánchez Maria Teresa, Ruiz-Alcaraz Antonio José, Blanco-Carnero José Eliseo, Sanchez-Campillo Maria, Parrilla Juan José, Larqué Elvira
Department of Physiology, Faculty of Biology, Campus Mare Nostrum, University of Murcia, Murcia 30100, Spain.
Obstetrics and Gynecology Service, Virgen de la Arrixaca Clinical Hospital, University of Murcia, Murcia 30120, Spain.
Int J Mol Sci. 2017 Jun 6;18(6):1203. doi: 10.3390/ijms18061203.
There is little information available on the effect of Gestational diabetes mellitus (GDM) treatment (diet or insulin) on placental lipid carriers, which may influence fetal fat accretion. Insulin may activate placental insulin receptors protein kinase (AKT) and extracellular signal regulated kinase ERK mediators, which might affect lipid metabolism. Placenta was collected from 25 control women, 23 GDM-Diet and 20 GDM-Insulin. Western blotting of insulin signaling mediators and lipid carriers was performed. The human choricarcinoma-derived cell line BeWo was preincubated with insulin inhibitors protein kinase (AKT) and extracellular signal regulated kinase (ERK) and ERK inhibitors to evaluate insulin regulation of lipid carriers. Maternal serum insulin at recruitment correlated to ultrasound fetal abdominal circumference in offspring of GDM and placental endothelial lipase (EL). Lipoprotein lipase in placenta was significantly reduced in both GDM, while most of the other lipid carriers tended to higher values, although not significantly. There was a significant increase in both phosphorylated-Akt and ERK in placentas from GDM-Insulin patients; both were associated to placental fatty acid translocase (FAT), fatty acid binding protein (A-FABP), and EL. BeWo cells treated with insulin pathway inhibitors significantly reduced A-FABP, fatty acid transport protein (FATP-1), and EL levels, confirming the role of insulin on these carriers. We conclude that insulin promotes the phosphorylation of placental insulin mediators contributing to higher levels of some specific fatty acid carriers in the placenta and fetal adiposity in GDM.
关于妊娠期糖尿病（GDM）治疗（饮食或胰岛素）对胎盘脂质载体的影响，目前可用信息较少，而胎盘脂质载体可能会影响胎儿脂肪堆积。胰岛素可能会激活胎盘胰岛素受体蛋白激酶（AKT）和细胞外信号调节激酶ERK介质，这可能会影响脂质代谢。从25名对照女性、23名接受饮食治疗的GDM患者和20名接受胰岛素治疗的GDM患者中采集胎盘。对胰岛素信号介质和脂质载体进行蛋白质免疫印迹分析。将人绒毛膜癌细胞系BeWo与胰岛素抑制剂蛋白激酶（AKT）、细胞外信号调节激酶（ERK）以及ERK抑制剂进行预孵育，以评估胰岛素对脂质载体的调节作用。招募时母体血清胰岛素水平与GDM患者后代的超声胎儿腹围以及胎盘内皮脂肪酶（EL）相关。在GDM患者中，胎盘脂蛋白脂肪酶显著降低，而大多数其他脂质载体的水平虽未显著升高，但有升高趋势。接受胰岛素治疗的GDM患者的胎盘磷酸化Akt和ERK均显著增加；二者均与胎盘脂肪酸转运蛋白（FAT）、脂肪酸结合蛋白（A-FABP）和EL相关。用胰岛素信号通路抑制剂处理的BeWo细胞显著降低了A-FABP、脂肪酸转运蛋白（FATP-1）和EL水平，证实了胰岛素对这些载体的作用。我们得出结论，胰岛素促进胎盘胰岛素介质的磷酸化，导致胎盘中某些特定脂肪酸载体水平升高以及GDM患者胎儿肥胖。
