IGF-1 LR3 Does Not Promote Growth in Late Gestation Growth Restricted Fetal Sheep.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM American journal of physiology. Endocrinology and metabolism Pub Date : 2024-12-16 DOI:10.1152/ajpendo.00259.2024
Alicia White, Jane Stremming, Stephanie R Wesolowski, Saif I Al-Juboori, Evgenia Dobrinskikh, Sean W Limesand, Laura D Brown, Paul J Rozance
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Abstract

Insulin-like growth factor-1 (IGF-1) and insulin are important fetal anabolic hormones. Complications of pregnancy, such as placental insufficiency, can lead to fetal growth restriction FGR) with low circulating IGF-1 and insulin concentrations and attenuated glucose-stimulated insulin secretion (GSIS), which likely contribute to neonatal glucose dysregulation. We previously demonstrated that a one-week infusion of IGF-1 LR3, an IGF-1 analog with low affinity for IGF binding proteins and high affinity for the IGF-1 receptor, at 6.6 μg·kg-1·hr-1 into normal fetal sheep increased body weight but lowered insulin concentrations and GSIS. In this study, FGR fetal sheep received either IGF-1 LR3 treatment at 1.17 ± 0.12 μg·kg-1·hr-1 (LR3; n=7) or vehicle (VEH; n=7) for one week. Plasma insulin, glucose, oxygen, and amino acids were measured before starting treatment and at the end of the treatment period. GSIS was measured on the final treatment day. Fetal body weights, insulin, glucose, oxygen, and GSIS were not different between groups. Amino acid concentrations decreased in LR3 (Baseline vs Final individual means comparison P=0.0232) but not in VEH (P=0.3866). In summary, a one-week IGF-1 LR3 treatment did not improve growth in FGR fetuses. Insulin concentrations and GSIS were not attenuated by IGF-1 LR3, yet circulating amino acids decreased, which could reflect increased amino acid utilization. We speculate that maintaining amino acid concentrations or raising insulin, glucose, and/or oxygen concentrations to values consistent with normally growing fetuses during IGF-1 LR3 treatment may be necessary to increase fetal growth in the setting of placental insufficiency and FGR.

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IGF-1 LR3 不会促进妊娠晚期生长受限胎羊的生长。
胰岛素样生长因子-1(IGF-1)和胰岛素是重要的胎儿合成代谢激素。妊娠并发症(如胎盘功能不全)可导致胎儿生长受限(FGR),循环中的 IGF-1 和胰岛素浓度较低,葡萄糖刺激的胰岛素分泌(GSIS)减弱,这可能会导致新生儿血糖失调。我们以前曾证实,向正常胎羊输注为期一周的 IGF-1 LR3(一种与 IGF 结合蛋白亲和力低而与 IGF-1 受体亲和力高的 IGF-1 类似物),剂量为 6.6 μg-kg-1-hr-1,可增加体重但降低胰岛素浓度和 GSIS。在这项研究中,FGR 胎羊接受 1.17 ± 0.12 μg-kg-1-hr-1 的 IGF-1 LR3 治疗(LR3;n=7)或药物治疗(VEH;n=7)一周。在开始治疗前和治疗结束时测量血浆胰岛素、葡萄糖、氧气和氨基酸。在治疗的最后一天测量GSIS。各组间的胎儿体重、胰岛素、葡萄糖、氧气和 GSIS 均无差异。LR3的氨基酸浓度下降(基线与最终个体均值比较,P=0.0232),但VEH的氨基酸浓度没有下降(P=0.3866)。总之,为期一周的IGF-1 LR3治疗并不能改善FGR胎儿的生长。IGF-1 LR3并未降低胰岛素浓度和GSIS,但循环中的氨基酸却减少了,这可能反映了氨基酸利用的增加。我们推测,在 IGF-1 LR3 治疗期间,维持氨基酸浓度或将胰岛素、葡萄糖和/或氧气浓度提高到与正常生长胎儿一致的值,可能是在胎盘功能不全和 FGR 的情况下增加胎儿生长所必需的。
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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
98
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.
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