IGF-1 LR3 does not promote growth in late-gestation growth-restricted fetal sheep.

White A, Stremming J, Wesolowski SR, Al-Juboori SI, Dobrinskikh E, Limesand SW, Brown LD, Rozance PJ

American journal of physiology. Endocrinology and metabolism16 Dec 2024Cited by 3 (Europe PMC)

PMID39679943PMCIDPMC11901354DOI10.1152/ajpendo.00259.2024PepBankPUB-39679943

Summary

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 1-wk 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·h^-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·h^-1 (LR3; n = 7) or vehicle (VEH; n = 7) for 1 wk. 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 1-wk 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.NEW & NOTEWORTHY IGF-1 LR3 treatment administered directly into growth-restricted fetal sheep circulation did not improve fetal growth or attenuate circulating insulin or fetal GSIS. Importantly, IGF-1 LR3 treatment reduced circulating amino acids, notably branched-chain amino acids, which have been shown to potentiate GSIS and protein accretion supporting fetal growth.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In growth-restricted fetal sheep, a 1-week IGF‑1 LR3 infusion did not change fetal body weight versus vehicle.
In plain wordsIn growth-restricted fetal sheep, IGF‑1 LR3 did not change fetal body weight compared with vehicle.
Peptide
IGF-1 LR3
Outcome
No significant changeFetal body weight
Study
sheepn = 14
Growth-restricted fetal sheep
Comparator
Vehicle
Outcome group
Body weight · Metabolic and weight
Studied dose
1.17 ± 0.12 µg/kg/h · infusion into fetal circulation · 1 weekAs given in this study (sheep).
Source sentences
Summary
Fetal body weights, insulin, glucose, oxygen, and GSIS were not different between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, FGR fetal sheep received either IGF-1 LR3 treatment at 1.17 ± 0.12 μg·kg^-1·h^-1 (LR3; n = 7) or vehicle (VEH; n = 7) for 1 wk.
Show in the study text Report a problemFND-3967994301
02AnimalAnimal study (in vivo)Efficacy outcome
In growth-restricted fetal sheep, IGF‑1 LR3 did not change plasma insulin concentrations versus vehicle.
In plain wordsIn growth-restricted fetal sheep, IGF‑1 LR3 did not change insulin levels compared with vehicle.
Peptide
IGF-1 LR3
Outcome
No significant changePlasma insulin
Study
sheepn = 14
Growth-restricted fetal sheep
Comparator
Vehicle
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
1.17 ± 0.12 µg/kg/h · infusion into fetal circulation · 1 weekAs given in this study (sheep).
Source sentences
Summary
Fetal body weights, insulin, glucose, oxygen, and GSIS were not different between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, FGR fetal sheep received either IGF-1 LR3 treatment at 1.17 ± 0.12 μg·kg^-1·h^-1 (LR3; n = 7) or vehicle (VEH; n = 7) for 1 wk.
Show in the study text Report a problemFND-3967994302
03AnimalAnimal study (in vivo)Efficacy outcome
In growth-restricted fetal sheep, IGF‑1 LR3 did not change plasma glucose concentrations versus vehicle.
In plain wordsIn growth-restricted fetal sheep, IGF‑1 LR3 did not change glucose levels compared with vehicle.
Peptide
IGF-1 LR3
Outcome
No significant changePlasma glucose
Study
sheepn = 14
Growth-restricted fetal sheep
Comparator
Vehicle
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.17 ± 0.12 µg/kg/h · infusion into fetal circulation · 1 weekAs given in this study (sheep).
Source sentences
Summary
Fetal body weights, insulin, glucose, oxygen, and GSIS were not different between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, FGR fetal sheep received either IGF-1 LR3 treatment at 1.17 ± 0.12 μg·kg^-1·h^-1 (LR3; n = 7) or vehicle (VEH; n = 7) for 1 wk.
Show in the study text Report a problemFND-3967994303
04AnimalAnimal study (in vivo)Efficacy outcome
In growth-restricted fetal sheep, IGF‑1 LR3 did not change oxygen measures versus vehicle.
In plain wordsIn growth-restricted fetal sheep, IGF‑1 LR3 did not change oxygen levels compared with vehicle.
Peptide
IGF-1 LR3
Outcome
No significant changeFetal oxygen
Study
sheepn = 14
Growth-restricted fetal sheep
Comparator
Vehicle
Outcome group
Pregnancy and fetal development · Whole body
Studied dose
1.17 ± 0.12 µg/kg/h · infusion into fetal circulation · 1 weekAs given in this study (sheep).
Source sentences
Summary
Fetal body weights, insulin, glucose, oxygen, and GSIS were not different between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, FGR fetal sheep received either IGF-1 LR3 treatment at 1.17 ± 0.12 μg·kg^-1·h^-1 (LR3; n = 7) or vehicle (VEH; n = 7) for 1 wk.
Show in the study text Report a problemFND-3967994304
05AnimalAnimal study (in vivo)Efficacy outcome
In growth-restricted fetal sheep, IGF‑1 LR3 did not change glucose-stimulated insulin secretion versus vehicle.
In plain wordsIn growth-restricted fetal sheep, IGF‑1 LR3 did not change the insulin response to glucose compared with vehicle.
Peptide
IGF-1 LR3
Outcome
No significant changeGlucose-stimulated insulin secretion (GSIS)
Study
sheepn = 14
Growth-restricted fetal sheep
Comparator
Vehicle
Outcome group
Glycemic control · Endocrine and hormones
Studied dose
1.17 ± 0.12 µg/kg/h · infusion into fetal circulation · 1 weekAs given in this study (sheep).
Source sentences
Summary
Fetal body weights, insulin, glucose, oxygen, and GSIS were not different between groups.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, FGR fetal sheep received either IGF-1 LR3 treatment at 1.17 ± 0.12 μg·kg^-1·h^-1 (LR3; n = 7) or vehicle (VEH; n = 7) for 1 wk.
Show in the study text Report a problemFND-3967994305
06AnimalAnimal study (in vivo)Mechanism
In growth-restricted fetal sheep, amino acid concentrations fell from baseline to the end of IGF‑1 LR3 treatment, but not with vehicle.
In plain wordsIn growth-restricted fetal sheep, amino acid levels fell during IGF‑1 LR3 treatment but not during vehicle.
Peptide
IGF-1 LR3
Outcome
DecreasePlasma amino acid concentrations
Study
sheepn = 14
Growth-restricted fetal sheep
Comparator
Baseline
Outcome group
Protein and amino acid metabolism · Metabolic and weight
Studied dose
1.17 ± 0.12 µg/kg/h · infusion into fetal circulation · 1 weekAs given in this study (sheep).
Source sentences
Summary
Amino acid concentrations decreased in LR3 (baseline vs. final individual means comparison P = 0.0232) but not in VEH (P = 0.3866).
2 context sentences(design, population, supporting numbers)
Summary · context
Plasma insulin, glucose, oxygen, and amino acids were measured before starting treatment and at the end of the treatment period.
Summary · context
In this study, FGR fetal sheep received either IGF-1 LR3 treatment at 1.17 ± 0.12 μg·kg^-1·h^-1 (LR3; n = 7) or vehicle (VEH; n = 7) for 1 wk.
Show in the study text Report a problemFND-3967994306
07AnimalAnimal study (in vivo)Mechanism
In growth-restricted fetal sheep, IGF‑1 LR3 treatment reduced circulating branched-chain amino acids.
In plain wordsIn growth-restricted fetal sheep, IGF‑1 LR3 lowered circulating branched-chain amino acids.
Peptide
IGF-1 LR3
Outcome
DecreaseBranched-chain amino acids
Study
sheepn = 14
Growth-restricted fetal sheep
Comparator
Vehicle
Outcome group
Protein and amino acid metabolism · Metabolic and weight
Studied dose
1.17 ± 0.12 µg/kg/h · infusion into fetal circulation · 1 weekAs given in this study (sheep).
Source sentences
Summary
IGF-1 LR3 treatment reduced circulating amino acids, notably branched-chain amino acids
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, FGR fetal sheep received either IGF-1 LR3 treatment at 1.17 ± 0.12 μg·kg^-1·h^-1 (LR3; n = 7) or vehicle (VEH; n = 7) for 1 wk.
Show in the study text Report a problemFND-3967994307

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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