Glucocorticoids impair fetal β-cell development in rats
Glucocorticoids impair fetal β-cell development in rats
复制标题
DOI：
10.1152/ajpendo.2001.281.3.e592
复制
发表时间：
2001-09-01
影响因子：
5.1
通讯作者：
Bráant, B
中科院分区：
文献类型：
--
作者：
Blondeau, B;Lesage, J;Bráant, B
在大鼠中，由于怀孕期间母体食物限制导致的胎儿生长不良与出生时β细胞质量下降和成年后葡萄糖耐受不良有关。在子宫内过度暴露于糖皮质激素可引起人类和动物的宫内生长迟缓和随后的啮齿动物葡萄糖耐受不良。本研究的目的是研究糖皮质激素过度暴露是否介导营养不良对β细胞质量的影响，并研究其在正常营养大鼠中的潜在作用。营养不良显著增加了母体和胎儿的皮质酮水平。营养不良的21日龄胎儿表现为生长迟缓和胰腺胰岛素含量降低；肾上腺切除术和皮下皮质酮植入阻止了母体皮质酮的增加，恢复了胎儿的β细胞质量。在营养正常的胎儿中，胎儿皮质酮水平与胎儿体重和胰岛素含量呈负相关；胎儿β细胞质量从假组的355 +/- 48马克增加到母体肾上腺切除术后的516 +/- 160马克；甲替拉酮对类固醇产生的抑制进一步增加到757 +/- 125马克杯。我们的数据支持糖皮质激素在胎儿β细胞发育中负作用的新概念。
In rats, poor fetal growth due to maternal food restriction during pregnancy is associated with decreased beta -cell mass at birth and glucose intolerance in adulthood. Overexposure to glucocorticoids in utero can induce intrauterine growth retardation in humans and animals and subsequent glucose intolerance in rodents. The aims of this study were to investigate whether glucocorticoid overexposure mediates the effect of undernutrition on beta -cell mass and to study their potential role in normally nourished rats. Undernutrition significantly increased maternal and fetal corticosterone levels. Twenty-one-day-old fetuses with undernutrition showed growth retardation and decreased pancreatic insulin content; adrenalectomy and subcutaneous corticosterone implants in their dams prevented the maternal corticosterone increase and restored fetal beta -cell mass. In fetuses with normal nutrition, fetal corticosterone levels were negatively correlated to fetal weight and insulin content; fetal beta -cell mass increased from 355 +/- 48 mug in sham to 516 +/- 160 mug after maternal adrenalectomy; inhibition of steroid production by metyrapone induced a further increase to 757 +/- 125 mug. Our data support the new concept of a negative role of glucocorticoids in fetal beta -cell development.