Glucose and amino acid kinetic response to graded  infusion of rhIGF-I in the late gestation ovine fetus

Liechty, Edward A.; Boyle, David W.; Moorehead, Helen; Lee, Wei Hua; Yang, Xiaolin; Denne, Scott C.

doi:10.1152/ajpendo.1999.277.3.e537

Cited by 12 publications

(14 citation statements)

References 18 publications

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“…Then, the fetus was infused with one of the following four infusates: 1) saline, 2) recombinant human (rh)IGF-I (gift of Eli Lilly Research Laboratories, Indianapolis, IN) plus a replacement dose of insulin (40 nmol IGF-I/h ϩ 16 mIU insulin/h), 3) insulin (890 mIU/h), and 4) IGF-I plus insulin (40 nmol IGF-I/h ϩ 890 mIU insulin/h). The infusion rates of insulin and IGF-I are similar to those of our previous work, have been shown to result in phamacological concentrations of insulin and IGF-I, and have been shown to affect amino acid and protein kinetics in the ovine fetus (4,30,31). The dose of insulin infused in group 2 was expected to maintain plasma insulin concentrations at the baseline level, counteracting the inhibition of insulin secretion during the rhIGF-I infusion.…”

Section: Methodssupporting

confidence: 54%

IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus

Shen

Mallon

Boyle

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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The mechanisms by which insulin-like growth factor I (IGF-I) and insulin regulate eukaryotic initiation factor (eIF)4F formation were examined in the ovine fetus. Insulin infusion increased phosphorylation of eIF4E-binding protein (4E-BP1) in muscle and liver. IGF-I infusion did not alter 4E-BP1 phosphorylation in liver. In muscle, IGF-I increased 4E-BP1 phosphorylation by 27%; the percentage in the gamma-form in the IGF-I group was significantly lower than that in the insulin group. In liver, only IGF-I increased eIF4G. Both IGF-I and insulin increased eIF4E. eIF4G binding in muscle, but only insulin decreased the amount of 4E-BP1 associated with eIF4E. In liver, only IGF-I increased eIF4E. eIF4G binding. Insulin increased the phosphorylation of p70 S6 kinase (p70(S6k)) in both muscle and liver and protein kinase B (PKB/Akt) in muscle, two indicative signal proteins in the phosphatidylinositol (PI) 3-kinase pathway. IGF-I increased PKB/Akt phosphorylation in muscle but had no effect on p70(S6k) phosphorylation in muscle or liver. We conclude that insulin and IGF-I modulate eIF4F formation; however, the two hormones have different regulatory mechanisms. Insulin increases phosphorylation of 4E-BP1 and eIF4E. eIF4G binding in muscle, whereas IGF-I regulates eIF4F formation by increasing total eIF4G. Insulin, but not IGF-I, decreased 4E-BP1 content associated with eIF4E. Insulin regulates translation initiation via the PI 3-kinase-p70(S6k) pathway, whereas IGF-I does so mainly via mechanisms independent of the PI 3-kinase-p70(S6k) pathway.

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Section: Methodssupporting

confidence: 54%

IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus

Shen

Mallon

Boyle

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…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).…”

Section: Discussionmentioning

confidence: 97%

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

Shen

Wisniowski

Denne

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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Fetal nutritional stress may result in intrauterine growth restriction and postnatal insulin resistance. To determine whether insulin resistance can begin in utero, we subjected late-gestation (130-135 days) ewes to 120 h of complete fasting and compared the results with our previous work in fed ewes (38). We determined the effect of insulin and/or recombinant human (rh)IGF-I infusion on ovine fetal phenylalanine kinetics, protein synthesis, and phenylalanine accretion. Experimental infusates were 1) saline, 2) rhIGF-I plus a replacement dose of insulin (40 nmol IGF-I/h + 16 mIU insulin/h), 3) insulin (890 mIU/h), and 4) IGF-I plus insulin (40 nmol IGF-I/h + 890 mIU insulin/h). During hormone infusion, both glucose and amino acid concentrations were clamped at basal concentrations. Amino acid infusion was required during infusion of either hormone to maintain plasma concentrations constant. However, the amount required during insulin infusion was less than during IGF-I infusion and 40% less than the amount required during identical studies in nonfasted animals. Phenylalanine used for protein synthesis and accretion was increased compared with control animals but again less so than in the nonfasted animals. In contrast to nonfasted animals, neither hormone increased the fractional synthetic rate of skeletal muscle protein nor that of plasma albumin. These results indicate that a short but severe nutritional stress can significantly alter the fetal anabolic response to insulin even when both glucose and amino acid substrate supplies are restored. Therefore, adaptive responses characterized by insulin resistance begin in utero when the fetus is subjected to sufficient nutritional stress.

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“…Further IGF-I infusion to fetal sheep results in anabolic effects with increased transplacental amino acid and glucose uptake and decreased fetal protein breakdown (34,35). In a recent study in mice, administration of IGF-I was associated with higher weight gain and higher endogenous IGF-I levels (36).…”

Section: Discussionmentioning

confidence: 99%

Influence of Insulin-Like Growth Factor I and Nutrition During Phases of Postnatal Growth in Very Preterm Infants

et al. 2011

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Pronounced growth restriction (GR) occurs after very preterm birth. The interaction between IGF-I, nutritional intake, and growth was evaluated prospectively in 64 infants with a mean (SD) GA of 25.7 (1.9) wk. Blood sampling of IGF-I and measurements of weight, length, and head circumference were performed weekly until discharge. Daily calculation of nutritional intake was performed. Standard deviation scores (SDSs) for growth parameters defined two growth phases: GR phase (birth until lowest SDS) and catch-up (CU) phase (lowest SDS until 35 gestational weeks). IGF-I concentrations during the first postnatal weeks were low and increased at 30 wk GA, irrespective of GA at birth, coinciding with initiation of CU growth. Concentrations of IGF-I were positively associated with change in weight SDS during the GR phase, p ϭ 0.001 and CU phase, p ϭ 0.004 -0.027. Protein and energy intake were not associated with change in SDS weight during the GR phase as opposed to the CU phase (p Ͻ 0.001, respectively). Nutritional intake did not correlate to concentrations of IGF-I before 30 wk GA. IGF-I is associated with growth at an earlier postnatal age than nutrient intake and the effect of nutrition on levels of IGF-I may be restricted to the period of established CU growth. T he maximum growth rate of the fetus is reached in the middle of pregnancy, where it is approximately three times higher than at term (1). Fetal growth rate is to a large extent determined by placental capacity of delivering nutrients to the fetus, whereas genetic influence seems to play a less important role. Placental function depends on the maternal nutritional state and the intrauterine endocrine environment. At preterm birth, the fetal-placental interaction is interrupted, which has an impact on continued extrauterine growth capacity. Postnatal growth retardation occurs almost inevitably after preterm birth and has been associated with decreased brain volumes and impaired neurodevelopmental outcome (2,3). Although attempts are made to optimize postnatal nutritional intakes in preterm infants, these are still commonly suboptimal according to intrauterine requirements (4). Increased postnatal nutritional intake has been shown to improve growth rate in very LBW infants (5), although a recent study could not demonstrate any apparent effect of hyperalimentation on subsequent postnatal growth in very preterm infants (6).IGF-I is an important fetal growth factor, which is essential for the developing brain (7). Concentrations of fetal IGF-I are closely related to placental transfer of glucose where fetal glucose increases insulin secretion, which in turn stimulates fetal IGF-I production (8). Fetal levels of IGF-I may also be regulated by an interaction at the feto-maternal placental interface (9). The disruption of placental nutrient supply after birth is followed by a rapid decrease in postnatal levels of IGF-I, suggesting a low endogenous production (10). While term infants restore their IGF-I levels within the first postnatal weeks, very prete...

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Glucose and amino acid kinetic response to graded infusion of rhIGF-I in the late gestation ovine fetus

Cited by 12 publications

References 18 publications

IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus

IGF-I and insulin regulate eIF4F formation by different mechanisms in muscle and liver in the ovine fetus

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

Influence of Insulin-Like Growth Factor I and Nutrition During Phases of Postnatal Growth in Very Preterm Infants

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