IGF-1 infusion increases growth in fetal sheep when euinsulinemia is maintained

in Journal of Endocrinology
Authors:
Jane Stremming Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

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https://orcid.org/0000-0002-8517-2463
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Eileen I Chang Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

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https://orcid.org/0000-0002-3444-7260
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Alicia White Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

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Paul J Rozance Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

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Laura D Brown Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA

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Correspondence should be addressed to J Stremming: jane.stremming@cuanschutz.edu
DOI:
https://doi.org/10.1530/JOE-24-0058
Volume/Issue:
Volume 262: Issue 1
Article Type:
Research Article
Article ID:
e240058
Online Publication Date:
07 Jun 2024
Copyright:
© the author(s) 2024
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Insulin-like growth factor 1 (IGF-1) is a critical fetal anabolic hormone. IGF-1 infusion to the normally growing sheep fetus increases the weight of some organs but does not consistently increase body weight. However, IGF-1 infusion profoundly decreases fetal plasma insulin concentrations, which may limit fetal growth potential. In this study, normally growing late-gestation fetal sheep received an intravenous infusion of either: IGF-1 (IGF), IGF-1 with insulin and dextrose to maintain fetal euinsulinemia and euglycemia (IGF+INS), or vehicle control (CON) for 1 week. The fetus underwent a metabolic study immediately prior to infusion start and after 1 week of the infusion to measure uterine and umbilical uptake rates of nutrients and oxygen. IGF+INS fetuses were 23% heavier than CON (P = 0.0081) and had heavier heart, liver, and adrenal glands than IGF and CON (P < 0.01). By design, final fetal insulin concentrations in IGF were 62% and 65% lower than IGF+INS and CON, respectively. Final glucose concentrations were similar in all groups. IGF+INS had lower final oxygen content than IGF and CON (P < 0.0001) and lower final amino acid concentrations than CON (P = 0.0002). Final umbilical oxygen uptake was higher in IGF+INS compared to IGF and CON (P < 0.05). Final umbilical uptake of several essential amino acids was higher in IGF+INS compared to CON (P < 0.05). In summary, maintaining euinsulinemia and euglycemia during fetal IGF-1 infusion is necessary to maximally support body growth. We speculate that IGF-1 and insulin stimulate placental nutrient transport to support fetal growth.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© the author(s) 2024
Article ID:
e240058
Article Type:
Research Article
Received Date:
20 Feb 2024
Accepted Date:
09 May 2024
Print Publication Date:
01 Jul 2024
Online Publication Date:
07 Jun 2024
Keywords:
fetal growth; insulin-like growth factor 1; insulin; amino acids; placental nutrient transport

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