Effect of type 2 diabetes mellitus on placental expression and activity of nutrient transporters and their association with birth weight and neonatal adiposity.
Effect of type 2 diabetes mellitus on placental expression and activity of nutrient transporters and their association with birth weight and neonatal adiposity.
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DOI：
10.1016/j.mce.2021.111319
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发表时间：
2021-07-15
影响因子：
4.1
通讯作者：
Powell TL
中科院分区：
文献类型：
--
作者：
Castillo-Castrejon M;Yamaguchi K;Rodel RL;Erickson K;Kramer A;Hirsch NM;Rolloff K;Jansson T;Barbour LA;Powell TL
患有 2 型糖尿病 (T2DM) 的女性所生的婴儿由于胎儿脂肪堆积过多而面临出生时大于胎龄的风险。胎盘营养转运决定胎儿营养的可用性，影响胎儿的生长。该研究的目的是评估 T2DM 对胎盘胰岛素信号、胎盘营养转运蛋白和新生儿肥胖的影响。胎盘采集自 BMI 匹配的血糖正常对照 (NGT，n=9) 和 T2DM (n=9) 女性。分离合体滋养层微绒毛（MVM）和基底（BM）质膜。测定了葡萄糖 (GLUT1, -4)、脂肪酸 (FATP2, -4, -6, FAT/CD36)、氨基酸 (SNAT1, -2, -4, LAT1, -2) 转运蛋白、胰岛素信号传导和系统 A 转运蛋白活性的表达。对 T2DM 女性所生新生儿的子集进行了新生儿脂肪量 (%) 测量。在 T2DM 的 BM 中，GLUT1 蛋白表达增加 (p=0.001)，GLUT4 蛋白表达减少 (p=0.006)。在 T2DM 和 NGT 组中，MVM FATP6 表达均增加 (p=0.02)，并与出生体重相关 (r=0.65，p=0.02)。 T2DM 中 BM FATP6 表达增加 (p=0.01)。在 T2DM 胎盘 MVM 中，SNAT1 表达增加 (p=0.05)，并与出生体重相关 (r=0.84，p=0.004)； SNAT2 增加 (p=0.01)，但系统 A 转运蛋白活性在各组之间没有差异。 MVM LAT1 表达在 T2DM 中增加 (p=0.01)，并与出生体重 (r=0.59，p=0.04) 和新生儿脂肪量 (r=0.76，p=0.06) 相关。在患有 T2DM 的妊娠中，葡萄糖、氨基酸和脂肪酸转运蛋白的胎盘蛋白表达增加，这可能导致胎儿生长加快和新生儿肥胖。
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.