Effects of intravenous insulin-like growth factor-I and insulin administration on insulin-like growth factor-binding proteins in the ovine fetus

Abstract

The insulin-like growth factors (IGF) are important anabolic hormones in the mammalian fetus; their anabolic actions are potentially modulated by alterations in the IGF-binding proteins (IGFBP). We have previously shown that the nutritional state of the fetus affects both IGF-I and the IGFBP concentrations. The present study was designed to determine the effect of alterations in insulin and IGF-I circulating concentrations on the IGFBPs. Because both insulin and IGF-I elicit decreases in glucose and amino acid concentrations, the concentrations of these substrates were clamped during the hormone infusions.Sixteen ovine fetuses were chronically catheterized at approximately 115 days of gestation, and experimental procedures performed at approximately 130 days of gestation. Insulin, IGF-I or both were infused for an 8-h period. Baseline concentrations of hormones and binding proteins were obtained, and concentrations were also obtained at the end of the infusion. Hepatic IGFBP-1 mRNA expression was also determined.Intravenous infusion of IGF-I significantly increased IGF-I concentrations in plasma in the ovine fetus. Intravenous infusion of insulin inhibited hepatic IGFBP-1 gene expression when amino acids and glucose were clamped. In contrast, intravenous infusion of recombinant human IGF-I (rhIGF-I) enhanced hepatic IGFBP-1 gene expression. Neither insulin nor rhIGF-I treatment had an effect on hepatic IGFBP-3 gene expression. Insulin did not alter plasma IGFBP-1 significantly, but it increased IGFBP-3 in plasma. rhIGF-I increased both IGFBP-1 and IGFBP-3 protein levels in plasma.The responses of IGFBP-1 and IGFBP-3 to increased plasma IGF-I and insulin may serve to protect the fetus from exaggerated anabolic effects and to blunt the hypoglycemic potential of circulating IGFs and insulin.

Acute IGF-I infusion stimulates protein synthesis in skeletal muscle and other tissues of neonatal pigs

“…Recently, circulating IGFBP-3 levels were shown to increase in the fetal sheep during an infusion of IGF-I in which circulating amino acid concentrations were maintained at the fasting level with our amino acid clamp technique (41). However, the rise in circulating IGF-I concentrations was much higher and the length of infusion was longer in that study than in the current study, and protein synthesis rates were not determined.…”

Amniotic IGF-I supplementation of growth-restricted fetal sheep alters IGF-I and IGF receptor type 1 mRNA and protein levels in placental and fetal tissues

“…However, in IGF-I-treated fetuses the increase was sevenfold, with lesser, but significant, increases in IGFBP-2 and IGFBP-3 mRNA levels also. Exogenous IGF administration to the ovine fetus has been reported to increase hepatic IGFBP-1 mRNA levels (Shen et al 2001), and this is a possibility here also. Alternatively, the altered amino acid metabolism by the gut, as described above, may have contributed to altered nutritional regulation of hepatic IGFBP production.…”

Anabolic effects of insulin and IGF-I in the ovine fetus are reduced by prolonged maternal fasting

“…We and others have documented that regulation of fetal growth results from a complex interaction between substrate supply and the resulting hormonal milieu (17,19,22,38,39). Our previous studies have demonstrated that glucose concentration was a significant factor determining amino acid catabolism and accretion (21,23).…”