Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA; Department of Obstetrics and Gynecology, Mie University, Mie, Japan.
Mol Cell Endocrinol. 2021 Jul 15;532:111319. doi: 10.1016/j.mce.2021.111319. Epub 2021 May 12.
Infants born to women with Type 2 Diabetes Mellitus (T2DM) are at risk of being born large for gestational age due to excess fetal fat accretion. Placental nutrient transport determines fetal nutrient availability, impacting fetal growth. The aims of the study were to evaluate the effect of T2DM on placental insulin signaling, placental nutrient transporters and neonatal adiposity.
Placentas were collected from BMI-matched normoglycemic controls (NGT, n = 9) and T2DM (n = 9) women. Syncytiotrophoblast microvillous (MVM) and basal (BM) plasma membranes were isolated. Expression of glucose (GLUT1, -4), fatty acid (FATP2, -4, -6, FAT/CD36), amino acid (SNAT1, -2, -4, LAT1, -2) transporters, insulin signaling, and System A transporter activity was determined. Neonatal fat mass (%) was measured in a subset of neonates born to T2DM women.
GLUT1 protein expression was increased (p = 0.001) and GLUT4 decreased (p = 0.006) in BM from T2DM. MVM FATP6 expression was increased (p = 0.02) and correlated with birth weight in both T2DM and NGT groups (r = 0.65, p = 0.02). BM FATP6 expression was increased (p = 0.01) in T2DM. In MVM of T2DM placentas, SNAT1 expression was increased (p = 0.05) and correlated with birth weight (r = 0.84, p = 0.004); SNAT2 was increased (p = 0.01), however System A transporter activity was not different between groups. MVM LAT1 expression was increased (p = 0.01) in T2DM and correlated with birth weight (r = 0.59, p = 0.04) and neonatal fat mass (r = 0.76, p = 0.06).
In pregnancies complicated by T2DM placental protein expression of transporters for glucose, amino acids and fatty acids is increased, which may contribute to increased fetal growth and neonatal adiposity.
由于胎儿脂肪过度堆积，患有 2 型糖尿病（T2DM）的女性所生婴儿有巨大儿的风险。胎盘营养物质转运决定了胎儿营养物质的可获得性，从而影响胎儿生长。本研究旨在评估 T2DM 对胎盘胰岛素信号、胎盘营养转运体和新生儿肥胖的影响。
从 BMI 匹配的正常血糖对照组（NGT，n=9）和 T2DM 组（n=9）女性中收集胎盘。分离合体滋养细胞微绒毛（MVM）和基底（BM）质膜。测定葡萄糖（GLUT1、-4）、脂肪酸（FATP2、-4、-6、FAT/CD36）、氨基酸（SNAT1、-2、-4、LAT1、-2）转运体、胰岛素信号和 System A 转运体活性的表达。在 T2DM 女性所生新生儿中测量新生儿脂肪量（%）。
T2DM 组 BM 中 GLUT1 蛋白表达增加（p=0.001），GLUT4 减少（p=0.006）。T2DM 和 NGT 组的 MVM FATP6 表达增加（p=0.02），与出生体重相关（r=0.65，p=0.02）。T2DM 组 BM 中 FATP6 表达增加（p=0.01）。T2DM 胎盘 MVM 中 SNAT1 表达增加（p=0.05），与出生体重相关（r=0.84，p=0.004）；SNAT2 增加（p=0.01），但两组间 System A 转运体活性无差异。T2DM 组 MVM LAT1 表达增加（p=0.01），与出生体重（r=0.59，p=0.04）和新生儿脂肪量（r=0.76，p=0.06）相关。
在 T2DM 合并妊娠中，胎盘葡萄糖、氨基酸和脂肪酸转运体的蛋白表达增加，这可能导致胎儿生长和新生儿肥胖增加。
