Effect of hyperinsulinemia on amino acid utilization in the ovine fetus

Thureen, Patti J.; Scheer, Bryan; Anderson, Susan M.; Tooze, Janet A.; Young, David A.; Hay, William W.

doi:10.1152/ajpendo.2000.279.6.e1294

Cited by 28 publications

(26 citation statements)

References 28 publications

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“…In contrast to this relatively blunted relationship among change in fetal arginine concentration, insulin secretion, and altered glucose metabolism, even small increases in insulin might produce an anabolic effect. For example, we have measured a direct and quite steep relationship between insulin concentrations and fetal utilization rates of most amino acids over the lower physiologic range of plasma insulin concentrations in late-gestation fetal sheep (31). Thus, a change in maternal arginine concentration sufficiently large to increase fetal arginine and insulin concentrations might have a definite anabolic effect on amino acid utilization in the fetus.…”

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Ovine Placental and Fetal Arginine Metabolism at Normal and Increased Maternal Plasma Arginine Concentrations

et al. 2002

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Arginine (A) may play a significant role in fetal growth, by stimulating insulin secretion and as a precursor for both polyamine synthesis and nitric oxide production. To determine whether increased maternal plasma A concentrations can enhance delivery of A to the fetus, uterine, umbilical, and net uteroplacental (UP) A uptake rates were measured in 12 pregnant ewes at 129.6 Ϯ 0.4 d gestation (mean Ϯ SEM) during normal and after 3 h of increased maternal plasma A concentrations. With a 2.7-fold increase in maternal plasma A concentrations (p Ͻ 0.001), there were significant increases in uterine A uptake (13.8 Ϯ 1.0 to 41.3 Ϯ 7.7 mol/min, p Ͻ 0.005), umbilical A uptake (3.3 Ϯ 0.5 to 5.2 Ϯ 0.8 mol·min Ϫ1 ·kg Ϫ1 fetus, p Ͻ 0.005), UP A uptake (17.8 Ϯ 6.2 to 89.2 Ϯ 20.3 mol·min Ϫ1 ·kg Ϫ1 placenta, p Ͻ 0.01), fetal arterial A concentration (98.7 Ϯ 6.3 to 137.1 Ϯ 9.9 M, p Ͻ 0.001), maternal A disposal rate (143.7 Ϯ 9.4 to 217.0 Ϯ 6.7 mol/min, p Ͻ 0.001), fetal A disposal rate (7.9 Ϯ 0.8 to 9.9 Ϯ 1.1 mol·min Ϫ1 ·kg Ϫ1 , p Ͻ 0.05), fetal A oxidation rate (1.31 Ϯ 0.24 to 1.84 Ϯ 0.36 mol·min Ϫ1 ·kg Ϫ1 , p Ͻ 0.05), and plasma insulin concentration in both fetus (16 Ϯ 2 to 20 Ϯ 2 U/mL, p Ͻ 0.001) and mother (24 Ϯ 3 to 32 Ϯ 4 U/mL, p Ͻ 0.001). Thus, increased maternal plasma A concentration increases maternal, UP, and fetal A net uptake, and increases insulin secretion in mother and fetus. The 4.2-fold larger increase in UP than net fetal A uptake could represent preferential UP A metabolism relative to fetal A metabolism, relatively limited placental-fetal A transport capacity compared with uterine A uptake capacity, or both; responsible mechanisms remain unknown. Arginine is a conditionally indispensable amino acid in the mammalian fetus and neonate (1, 2), and maintenance of fetal arginine supply and plasma concentrations are important for optimal fetal growth. The mechanisms by which arginine promotes fetal growth, however, are multifaceted and have not been adequately investigated. Arginine is an insulin secretagogue in ovine and human fetuses (3-7) and in human newborns (8 -10); thus the role of arginine in fetal growth may include an insulin-mediated anabolic effect. In addition, arginine could stimulate growth as a precursor for polyamine synthesis (11) and nitric oxide production (12-14).In contrast, arginine deficiency has been shown to induce growth restriction in experimental animals (15, 16). A potential therapy for fetal growth restriction, therefore, could include maternal plasma arginine supplementation in an attempt to increase fetal arginine supply. It is not known, however, whether increasing maternal plasma arginine concentration could increase net fetal arginine uptake, fetal plasma arginine concentration, or fetal insulin concentration. In addition, the characteristics of placental arginine uptake, metabolism, and transport to the fetus have not been determined. Therefore, this study was designed to determine how maternal arginine supplementation affects maternal, uteroplacental, and fetal arginine net ...

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Ovine Placental and Fetal Arginine Metabolism at Normal and Increased Maternal Plasma Arginine Concentrations

et al. 2002

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“…Both of these values are within the physiologic range of postfeeding insulin concentrations. Similarly, a hyperinsulinemic, euaminoacidemic clamp in fetal sheep demonstrated that physiologic increases in plasma insulin concentration increased net amino acid and nitrogen utilization rates in the ovine fetus independent of plasma glucose and amino acid concentrations, and the insulin concentration required to achieve the halfmaximal amino acid utilization rate ranged from 6 to 16 U/mL for the essential amino acids (48). Additionally, it was estimated that two thirds of the increased leucine utilization rate was insulinspecific and one third was attributable to the increase in plasma leucine concentration.…”

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Effect of Low versus High Intravenous Amino Acid Intake on Very Low Birth Weight Infants in the Early Neonatal Period

Thureen

2003

Pediatric Research

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Greater protein intakes are required than have been commonly used to achieve fetal in utero protein accretion rates in preterm neonates. To study the efficacy and safety of more aggressive amino acid intake, we performed a prospective randomized study in 28 infants [mean wt, 946 Ϯ 40 g (SEM)] of 1 (low amino acid intake, LAA) versus 3 g·kg Ϫ1 ·d Ϫ1 (high amino acid intake, HAA) at 52.0 Ϯ 3.0 h of life. After a minimum of 12 h of parenteral nutrition, efficacy was determined by protein balance and was significantly lower in the LAA versus HAA groups by both nitrogen balance (Ϫ0. Abbreviations PN, parenteral nutrition LAA, low amino acid intake HAA, high amino acid intake Int leuc , leucine intake rate Q leuc , leucine flux rate Ox leuc , leucine oxidation rate NOD leuc , nonoxidative leucine disposal intake rate RP leuc , rate of leucine appearance from protein breakdown ELBW, extremely low birth weight BUN, blood urea nitrogen GCMS, gas chromatography-mass spectroscopyThe current standard for postnatal nutrition in all preterm infants is one that duplicates normal in utero fetal growth rates (1). Owing to advances in perinatal care, more very preterm infants are surviving. These infants have unique nutritional metabolic requirements for growth, predicted by low energy stores, high protein flux rate, and a high metabolic rate as a result of a relatively larger mass of metabolically active organs. Nevertheless, it is common practice in many neonatal intensive care units to limit nutrient administration, particularly amino acids, to ELBW or sick neonates in the early neonatal period because of concerns of substrate intolerance. Several studies suggest that this delay in nutrition results in postnatal malnutrition that produces measurable growth failure at hospital discharge (2-4).Although strategies to improve growth necessitate delivery of larger amounts of both energy and protein beginning shortly after birth, there are reasons to suggest that focusing on protein delivery may be particularly important. Throughout life, maximal weight-specific protein gain occurs before 32 wk gestation (5). Data from studies in fetal animal models suggest that amino acid metabolic rates may be a much more sensitive indicator than growth rate of adequate nutrition before term (6). Additionally, recent data suggest that long-term developmental outcome in the preterm may be correlated with early protein intake (7

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“…During late gestation, insulin stimulates amino acid utilization, whole body protein accretion, and skeletal muscle fractional protein synthesis under conditions of amino acid sufficiency (10,30,41,44). The fetus also responds to an amino acid infusion by increasing protein synthesis and accretion (24).…”

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Insulin is required for amino acid stimulation of dual pathways for translational control in skeletal muscle in the late-gestation ovine fetus

Brown¹,

Rozance²,

Barry³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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Effect of hyperinsulinemia on amino acid utilization in the ovine fetus

Cited by 28 publications

References 28 publications

Ovine Placental and Fetal Arginine Metabolism at Normal and Increased Maternal Plasma Arginine Concentrations

Ovine Placental and Fetal Arginine Metabolism at Normal and Increased Maternal Plasma Arginine Concentrations

Effect of Low versus High Intravenous Amino Acid Intake on Very Low Birth Weight Infants in the Early Neonatal Period

Insulin is required for amino acid stimulation of dual pathways for translational control in skeletal muscle in the late-gestation ovine fetus

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