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

J Endocrinol. 2024 May 1:JOE-24-0058. doi: 10.1530/JOE-24-0058. Online ahead of print.

Abstract

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 one week. The fetus underwent a metabolic study immediately prior to infusion start and after one 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 hearts, livers, 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.