Insulin-like growth factor 1 alters feto-placental protein and carbohydrate metabolism in fetal sheep.

Abstract

Insulin-like growth factor 1 (IGF-1) is an anabolic hormone in postnatal life and may be an important endocrine regulator of fetal growth. However, its effects on fetal metabolism in vivo have not previously been determined. We studied the effect of 50 micrograms/h.kg IGF-1 infusion in 12 chronically catheterized fetal sheep. Fetal blood amino nitrogen concentrations fell 10% and maternal 7%, consistent with a rise in feto-placental amino acid uptake. Fetal amino acid oxidation, measured by fetal urea production fell by 30% (44.4 +/- 10.5 to 30.9 +/- 8.0 mumol/min). Fetal and maternal blood glucose concentrations both fell by 0.1 mM, consistent with increased feto-placental glucose uptake. Placental lactate production fell 30% (114 +/- 15 to 78 +/- 11 mumol/min), as did fetal and uterine lactate uptake. There was no change in umbilical or uterine blood flows, nor in placental transfer by simple or facilitated diffusion. We conclude that IGF-1 has anabolic effects on feto-placental protein and carbohydrate metabolism. Circulating IGF-1 may in part mediate the regulation of fetal growth in response to fetal nutrient supply.

The IGF Axis in Baboon Pregnancy: Placental and Systemic Responses to Feeding 70% Global Ad Libitum Diet

“…The fetus regulates placental function through signals it sends to the placenta. Insulin-like growth factors (IGFs: IGF-I and -II), high affinity IGF binding proteins (IGFBPs), and related IGF receptors (IGF-1R and IGF-2R) comprise part of the complex communication network between mother, placenta, and fetus [2]. IGFs influence autocrine and paracrine regulation of cell proliferation, migration, and survival.…”

Early developmental influences on hepatic organogenesis

“…31,32 Growth factors play a major role in the maturation of organ systems prior to birth. 17 For example, in the fetus, IGFs, synthesized by the placenta and fetal liver, 33 mediate growth 34 under the regulation of glucose and insulin. 35 The ontogenies of a number of genes that have a critical role in regulating both liver growth and development in utero, as well as postnatal growth and endocrine sensitivity, 36,37 have recently been determined in the sheep.…”

Whole-body fuel selection: ‘reproduction’

“…With regard to the influence of IGF-1 on fetal growth, recent studies indicate that in contrast to chronic hyperinsulinaemia, which has variable effects on the growth of major fetal organs (Susa et al 1984;Milley, 1986), long-term IGF-1 administration enhances the growth of fetal heart, kidney, liver and lung . Its stimulatory effect on fetal growth is accompanied by a reduction in fetal amino acid oxidation, enhanced feto-placental amino acid and glucose uptake with no change in uterine or umbilical blood flow, thus leading Harding et al (1994) to conclude that IGF-1 has anabolic effects on fetoplacental protein and carbohydrate metabolism. Although IGF-1 increases the proportion and surface area of fetal trophectoderm in the placenta and, therefore, the potential for an enhanced rate of nutrient transfer across the placenta, no increase in either simple or facilitated placental diffusion was observed by Harding et al (1994).…”

“…Its stimulatory effect on fetal growth is accompanied by a reduction in fetal amino acid oxidation, enhanced feto-placental amino acid and glucose uptake with no change in uterine or umbilical blood flow, thus leading Harding et al (1994) to conclude that IGF-1 has anabolic effects on fetoplacental protein and carbohydrate metabolism. Although IGF-1 increases the proportion and surface area of fetal trophectoderm in the placenta and, therefore, the potential for an enhanced rate of nutrient transfer across the placenta, no increase in either simple or facilitated placental diffusion was observed by Harding et al (1994). Of course, the IGFs are bound to specific proteins which, depending on the circumstances, may either inhibit or enhance IGF action.…”