Sensitivity to metabolic signals in late-gestation growth-restricted fetuses from rapidly growing adolescent sheep.

Sensitivity to metabolic signals in late-gestation growth-restricted fetuses from rapidly growing adolescent sheep.
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快速生长的青春期绵羊妊娠晚期生长受限的胎儿对代谢信号的敏感性。

DOI:
10.1152/ajpendo.00294.2007
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发表时间:
2007
期刊:
American journal of physiology. Endocrinology and metabolism
影响因子:
--
通讯作者:
HayJr,WilliamW
HayJr,WilliamW
中科院分区:
--
文献类型:
--
作者:
Wallace,JacquelineM;Milne,JohnS;Aitken,RaymondP;HayJr,WilliamW

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在胎儿高胰岛素-正常血糖(HI-euG,n= 18)和高血糖-正常胰岛素(HG-euI,n= 12)钳夹期间研究胎儿对胰岛素和葡萄糖的敏感性。对单胎青春期母羊饲喂高(H)或对照(C)营养摄入量,以分别诱导受损或正常的胎盘/胎儿大小。导管插入脐静脉(v)、胎儿动脉(a)和静脉,研究在妊娠第126天和第133天之间进行。采用稳态经胎盘扩散法测定脐血流量(UmBF),采用Fick原理定量葡萄糖流量。对于HI-euG研究,在自发发生的胎儿胰岛素浓度和另外两个较高水平下测量胎儿葡萄糖利用率,而将胎儿葡萄糖钳制在初始基线水平。在HG-euI研究中,胎儿胰岛素被生长抑素抑制,在基线(生长抑素前)葡萄糖浓度和该值的150%和200%时测定胎儿葡萄糖利用率。H组的胎盘重量(219 vs. 395 g)、胎儿重量(2,965 vs. 4,373 g)和UmBF(519 vs. 794 ml/min)低于C组(P< 0.001)。相对于对照胎仔,生长受限胎仔在非扰动状态下的葡萄糖提取率(G[v − a]/G[v] × 100)较高(21.7 vs. 15.9%),尽管葡萄糖(0.78 vs. 1.05 μmol/ml)和胰岛素(8.5 vs. 16.9 μU/ml)浓度较低(均P < 0.001)。在HI-euG研究期间,总胎儿葡萄糖利用率随胰岛素浓度升高而升高(H组和C组分别为65%和64%)。同样,在HG-euI研究中,葡萄糖供应增加2倍,H组和C组的胎儿葡萄糖利用率分别增加41%和44%。在两项研究中,H组与C组相比,绝对总胎儿葡萄糖利用率降低每公斤胎仔表达量差异无显著性(P> 0.05),但差异无显著性(P> 0.01)(HI-euG:34.7、49.5和57.5,在H中; 34.7、51.2和56.1 μmol·min−1·kg− 1,在C中; HG-euI:28.7、35.7和40.8,在H中; 32.9、34.5和43.8 μmol·min−1·kg− 1,在C中)。这些正常体重特定的代谢反应,以短期实验增加血浆胰岛素和葡萄糖在慢性IUGR的反应表明维持机制的胰岛素作用和葡萄糖的摄取/利用能力,如果持续存在,可能会使这种IUGR后代在以后的生活中过度的能量沉积。
Fetal sensitivity to insulin and glucose was investigated during fetal hyperinsulinemic-euglycemic (HI-euG,n= 18) and hyperglycemic-euinsulinemic (HG-euI,n= 12) clamps. Singleton bearing adolescent ewes were fed high (H) or control (C) nutrient intakes to induce compromised or normal placental/fetal size, respectively. Catheters were inserted in the umbilical vein (v), fetal artery, (a) and veins, and studies were conducted betweenday 126and133of gestation. Umbilical blood flow (UmBF) was determined by the steady-state transplacental diffusion technique using3H2O, and glucose fluxes were quantified by the Fick principle. For the HI-euG study, fetal glucose utilization was measured at spontaneously occurring fetal insulin concentrations and two additional higher levels, whereas fetal glucose was clamped at the initial baseline level. For the HG-euI study, fetal insulin was suppressed by somatostatin infusion, and fetal glucose utilization was determined at baseline (before somatostatin) glucose concentrations, and at 150 and 200% of this value. Placentome weight (219 vs. 395 g), fetal weight (2,965 vs. 4,373 g), and UmBF (519 vs. 794 ml/min) were lower (P< 0.001) in H than in C groups. Relative to control fetuses, glucose extraction (G[v − a]/G[v] × 100) in the nonperturbed state was higher (21.7 vs. 15.9%) in growth-restricted fetuses despite lower glucose (0.78 vs. 1.05 μmol/ml) and insulin (8.5 vs. 16.9 μU/ml) concentrations (allP< 0.001). During the HI-euG study, total fetal glucose utilization rate increased in response to higher insulin concentrations (65 and 64% in H and C groups). Similarly during the HG-euI study, a twofold increase in glucose supply increased fetal glucose utilization by 41 and 44% in H and C groups, respectively. Throughout both studies, absolute total fetal glucose utilization rates were reduced in H vs. C groups (P< 0.01) but were similar when expressed per kilogram fetus (HI-euG: 34.7, 49.5, and 57.5 in H vs. 34.7, 51.2, and 56.1 μmol·min−1·kg−1in C, HG-euI: 28.7, 35.7, and 40.8 in H vs. 32.9, 34.5, and 43.8 μmol·min−1·kg−1in C). These normal body weight-specific metabolic responses to short-term experimental increases in plasma insulin and glucose in response to chronic IUGR indicate maintained mechanisms of insulin action and glucose uptake/utilization capacity, which, if persistent, might predispose such IUGR offspring to excessive energy deposition in later life.
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