Owens Julie A, Gatford Kathryn L, De Blasio Miles J, Edwards Lisa J, McMillen I Caroline, Fowden Abigail L
Department of Physiology, University of Adelaide, SA, Australia.
J Physiol. 2007 Nov 1;584(Pt 3):935-49. doi: 10.1113/jphysiol.2007.142141. Epub 2007 Aug 30.
Restricted growth before birth is associated with impaired insulin secretion but with initially enhanced insulin sensitivity in early postnatal life, which then progresses to insulin resistance and impaired glucose homeostasis by adulthood. This suggests that prenatal restraint impairs insulin secretion, but increases insulin sensitivity, before birth. Poor placental growth and function are major causes of restricted fetal growth in humans. We have therefore investigated the effects of restricted placental growth and function on plasma glucose, alpha-amino nitrogen and insulin concentrations and glucose- and arginine-stimulated insulin secretion in the fetal sheep at 120 and 140 days gestational age, and on insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp, at 130 days gestational age. Placental restriction decreased fetal blood pH and oxygen content, and weight in late gestation by approximately 20%. Reduced fetal and placental weights and indices of poor placental function, in particular fetal hypoxia and hypoglycaemia, were associated with impaired glucose- and arginine-stimulated insulin secretion, but not with changes in insulin sensitivity in the fetal sheep. We conclude that the impaired insulin secretion capacity reported in children and adults after intrauterine growth restriction, and in the neonatal and young adult sheep which is small at birth, is present in utero and persists. Whether this reflects the actions of the adverse intrauterine environment or changes to intrinsic capacity is unclear, but in utero interventions may be necessary to improve postnatal insulin secretion in the infant who is growth-restricted before birth.
出生前生长受限与胰岛素分泌受损有关，但在出生后早期胰岛素敏感性最初增强，随后在成年期发展为胰岛素抵抗和葡萄糖稳态受损。这表明产前受限在出生前会损害胰岛素分泌，但会增加胰岛素敏感性。胎盘生长和功能不良是人类胎儿生长受限的主要原因。因此，我们研究了胎盘生长和功能受限对妊娠120天和140天的胎羊血浆葡萄糖、α-氨基氮和胰岛素浓度以及葡萄糖和精氨酸刺激的胰岛素分泌的影响，以及在妊娠130天通过高胰岛素正常血糖钳夹测量的胰岛素敏感性。胎盘受限降低了胎儿血液pH值和氧含量，妊娠晚期胎儿体重下降约20%。胎儿和胎盘重量减轻以及胎盘功能不良指标，特别是胎儿缺氧和低血糖，与葡萄糖和精氨酸刺激的胰岛素分泌受损有关，但与胎羊胰岛素敏感性变化无关。我们得出结论，宫内生长受限后儿童和成人以及出生时体重较小的新生和年轻成年绵羊中报道的胰岛素分泌能力受损在子宫内就已存在并持续存在。这是否反映了不良宫内环境的作用或内在能力的变化尚不清楚，但对于出生前生长受限的婴儿，可能需要进行宫内干预以改善出生后的胰岛素分泌。
