scholarly journals Prolonged amino acid infusion into intrauterine growth-restricted fetal sheep increases leucine oxidation rates

2018 ◽  
Vol 315 (6) ◽  
pp. E1143-E1153 ◽  
Author(s):  
Sandra G. Wai ◽  
Paul J. Rozance ◽  
Stephanie R. Wesolowski ◽  
William W. Hay ◽  
Laura D. Brown
Keyword(s):  
Amino Acid ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Fetal Sheep ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Intrauterine Growth ◽  
Leucine Oxidation ◽  
Fetal Plasma ◽  
Oxidation Rates

Overcoming impaired growth in an intrauterine growth-restricted (IUGR) fetus has potential to improve neonatal morbidity, long-term growth, and metabolic health outcomes. The extent to which fetal anabolic capacity persists as the IUGR condition progresses is not known. We subjected fetal sheep to chronic placental insufficiency and tested whether prolonged amino acid infusion would increase protein accretion in these IUGR fetuses. IUGR fetal sheep were infused for 10 days with either mixed amino acids providing ~2 g·kg−1·day−1 (IUGR-AA) or saline (IUGR-Sal) during late gestation. At the end of the infusion, fetal plasma leucine, isoleucine, lysine, methionine, and arginine concentrations were higher in the IUGR-AA than IUGR-Sal group ( P < 0.05). Fetal plasma glucose, oxygen, insulin, IGF-1, cortisol, and norepinephrine concentrations were similar between IUGR groups, but glucagon concentrations were fourfold higher in the IUGR-AA group ( P < 0.05). Net umbilical amino acid uptake rate did not differ between IUGR groups; thus the total amino acid delivery rate (net umbilical amino acid uptake + infusion rate) was higher in the IUGR-AA than IUGR-Sal group (30 ± 4 vs. 19 ± 1 μmol·kg−1·min−1, P < 0.05). Net umbilical glucose, lactate, and oxygen uptake rates were similar between IUGR groups. Fetal leucine oxidation rate, measured using a leucine tracer, was higher in the IUGR-AA than IUGR-Sal group (2.5 ± 0.3 vs. 1.7 ± 0.3 μmol·kg−1·min−1, P < 0.05). Fetal protein accretion rate was not statistically different between the IUGR groups (1.6 ± 0.4 and 0.8 ± 0.3 μmol·kg−1·min−1 in IUGR-AA and IUGR-Sal, respectively) due to variability in response to amino acids. Prolonged amino acid infusion into IUGR fetal sheep increased leucine oxidation rates with variable anabolic response.

Removal of infused amino acids by splanchnic and leg tissues in humans

1986 ◽  
Vol 250 (4) ◽  
pp. E407-E413 ◽  
Author(s):  
R. A. Gelfand ◽  
M. G. Glickman ◽  
R. Jacob ◽  
R. S. Sherwin ◽  
R. A. DeFronzo
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Uptake ◽  
Branched Chain Amino Acids ◽  
Acid Uptake ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Significant Uptake ◽  
Branched Chain

To compare the contributions of splanchnic and skeletal muscle tissues to the disposal of intravenously administered amino acids, regional amino acid exchange was measured across the splanchnic bed and leg in 11 normal volunteers. Postabsorptively, net release of amino acids by leg (largely alanine and glutamine) was complemented by the net splanchnic uptake of amino acids. Amino acid infusion via peripheral vein (0.2 g X kg-1 X h-1) caused a doubling of plasma insulin and glucagon levels and a threefold rise in blood amino acid concentrations. Both splanchnic and leg tissues showed significant uptake of infused amino acids. Splanchnic tissues accounted for approximately 70% of the total body amino acid nitrogen disposal; splanchnic uptake was greatest for the glucogenic amino acids but also included significant quantities of branched-chain amino acids. In contrast, leg amino acid uptake was dominated by the branched-chain amino acids. Based on the measured leg balance, body skeletal muscle was estimated to remove approximately 25-30% of the total infused amino acid load and approximately 65-70% of the infused branched-chain amino acids. Amino acid infusion significantly stimulated both the leg efflux and the splanchnic uptake of glutamine (not contained in the infusate). We conclude that when amino acids are infused peripherally in normal humans, splanchnic viscera (liver and gut) are the major sites of amino acid disposal.

scholarly journals Acute supplementation of amino acids increases net protein accretion in IUGR fetal sheep

2012 ◽  
Vol 303 (3) ◽  
pp. E352-E364 ◽  
Author(s):  
Laura D. Brown ◽  
Paul J. Rozance ◽  
Stephanie R. Thorn ◽  
Jacob E. Friedman ◽  
William W. Hay
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Insulin Signaling ◽  
Acid Uptake ◽  
Protein Breakdown ◽  
Fetal Sheep ◽  
Leucine Oxidation ◽  
Oxidation Rates ◽  
Breakdown Rates ◽  
Accretion Rates

Placental insufficiency decreases fetal amino acid uptake from the placenta, plasma insulin concentrations, and protein accretion, thus compromising normal fetal growth trajectory. We tested whether acute supplementation of amino acids or insulin into the fetus with intrauterine growth restriction (IUGR) would increase net fetal protein accretion rates. Late-gestation IUGR and control (CON) fetal sheep received acute, 3-h infusions of amino acids (with euinsulinemia), insulin (with euglycemia and euaminoacidemia), or saline. Fetal leucine metabolism was measured under steady-state conditions followed by a fetal muscle biopsy to quantify insulin signaling. In CON, increasing amino acid delivery rates to the fetus by 100% increased leucine oxidation rates by 100%. In IUGR, amino acid infusion completely suppressed fetal protein breakdown rates but increased leucine oxidation rate by only 25%, resulting in increased protein accretion rates by 150%. Acute insulin infusion, however, had very little effect on amino acid delivery rates, fetal leucine disposal rates, or fetal protein accretion rates in CON or IUGR fetuses despite robust signaling of the fetal skeletal muscle insulin-signaling cascade. These results indicate that, when amino acids are given directly into the fetal circulation independently of changes in insulin concentrations, IUGR fetal sheep have suppressed protein breakdown rates, thus increasing net fetal protein accretion.

Decreased amino acid uptake by erythrocytes during postoperative sepsis

1995 ◽  
Vol 41 (3) ◽  
pp. 462-464 ◽  
Author(s):  
N B Roberts ◽  
R Wilkes
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Amino Acid Uptake ◽  
Acid Uptake ◽  
Postoperative Sepsis ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Amino Acid Utilization

Abstract We describe a patient with postoperative sepsis associated with reduced ability to transport amino acids into erythrocytes. Administration of amino acid infusion showed no effect on plasma or red blood cell concentrations of the amino acids during the sepsis period. However, when the site of sepsis was removed, patient recovery was associated with marked increases of all amino acids, particularly in the red blood cells. The case illustrates the potential of red blood cells as a marker of amino acid utilization and demonstrates the association of sepsis with effects on cellular uptake.

scholarly journals Net Hepatic Gluconeogenic Amino Acid Uptake in Response to Peripheral versus Portal Amino Acid Infusion in Conscious Dogs

1999 ◽  
Vol 129 (12) ◽  
pp. 2218-2224 ◽  
Author(s):  
Mary Courtney Moore ◽  
Po-Shiuan Hsieh ◽  
Paul J. Flakoll ◽  
Doss W. Neal ◽  
Alan D. Cherrington
Keyword(s):  
Amino Acid ◽  
Amino Acid Uptake ◽  
Conscious Dogs ◽  
Acid Uptake ◽  
Acid Infusion ◽  
Amino Acid Infusion

Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep

2005 ◽  
Vol 289 (4) ◽  
pp. R1099-R1106 ◽  
Author(s):  
Amanda C. Boyce ◽  
Karen J. Gibson ◽  
E. Marelyn Wintour ◽  
Irene Koukoulas ◽  
Eugenie R. Lumbers
Keyword(s):  
Amino Acid ◽  
Renin Angiotensin System ◽  
Sodium Reabsorption ◽  
Mrna Levels ◽  
Renal Growth ◽  
Fetal Sheep ◽  
Angiotensin System ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Glomerulotubular Balance

These experiments examined whether renal growth and the fetal renin-angiotensin system could be stimulated by infusion of amino acids and whether chronic amino acid infusions restored glomerulotubular balance, which had been disrupted during 4-h infusions. Five fetal sheep aged 122 ± 1 days gestation received an infusion of alanine, glycine, proline and serine in 0.15 M saline at 0.22 mmol/min for 7 days. Six control fetuses were given saline at the same rate (5 ml/h). Kidney wet weights after amino acid infusion were 28% larger than control fetuses ( P < 0.05), and renal angiotensinogen mRNA levels were ∼2.6-fold higher ( P < 0.005). Circulating renin levels and renal renin mRNA levels were suppressed ( P < 0.05), and renal renin protein levels tended to be lower. Arterial pressure was increased, and there was a marked, sustained natriuresis and diuresis. Glomerular filtration rate and filtered sodium were ∼two-fold higher throughout infusion ( P < 0.05). Fractional proximal sodium reabsorption, suppressed at 4 h (from 73.4 ± 6.5 to 53.7 ± 10.2%), did not return to control levels (36.1 ± 3.4% on day 7, P < 0.05). Distal sodium reabsorption was markedly increased (from 79 ± 25 to 261 ± 75 μmol/min by day 7, P < 0.005), but this was not sufficient to restore glomerulotubular balance. The resultant high rates of sodium excretion led to hyponatremia and polyhydramnios. In conclusion, long-term amino acid infusions increased renal angiotensinogen gene expression, kidney weight, and distal nephron sodium reabsorptive capacity but failed to restore proximal and total glomerulotubular balance.

scholarly journals Effect of IGF-I on serine metabolism in fetal sheep

2000 ◽  
Vol 165 (2) ◽  
pp. 261-269 ◽  
Author(s):  
EC Jensen ◽  
P van Zijl ◽  
PC Evans ◽  
JE Harding
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Amino Acid Uptake ◽  
Acid Synthesis ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Amino Acid Synthesis ◽  
Fetal Sheep ◽  
Igf I

Acute infusion of IGF-I to the fetus has been shown to inhibit amino acid oxidation and appears to increase fetoplacental amino acid uptake. This study was designed to investigate further the effects of IGF-I on fetal amino acid metabolism. Radiolabeled serine was used to test the hypothesis that fetal IGF-I infusion enhances serine uptake into the fetus and/or placenta and inhibits serine oxidation. Eight fetal sheep were studied at 127 days of gestation before and during a 4-h infusion of IGF-I (50 microg/h per kg). During the infusion there was no change in uptake of serine or its oxidation by fetus or placenta. However, both uptake and oxidation of serine and glycine decreased in the fetal carcass. There was also a decrease in fetal blood serine and glycine concentrations which could indicate a decrease in protein breakdown, although reduced amino acid synthesis cannot be excluded. Thus IGF-I appeared to influence the distribution of these amino acids as oxidative substrates between different fetal tissues. In addition, fetal IGF-I infusion increased the conversion of serine to glycine which is likely to have increased the availability of one-carbon groups for biosynthesis. Our data provide further evidence that IGF-I plays a role in the regulation of fetoplacental amino acid metabolism.

Renal responses to amino acids in the sheep fetus

1996 ◽  
Vol 270 (6) ◽  
pp. R1226-R1230 ◽  
Author(s):  
L. L. Woods ◽  
A. R. Hohimer ◽  
L. E. Davis
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Intake ◽  
Amino Nitrogen ◽  
Maternal Plasma ◽  
Fetal Sheep ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Nitrogen Levels ◽  
Amino Acid Levels

Adult animals and humans are known to increase renal blood flow and glomerular filtration rate (GFR) in response to an acute protein load or amino acid infusion; however, the ontogeny of this phenomenon is not known. This study was designed to test the hypothesis that, despite normally high baseline amino acid levels in the fetus, increases in plasma amino acids stimulate increases in GFR before birth. Eight chronically instrumented fetal sheep (126 +/- 1 days gestation) were infused with a mixture of amino acids (0.15 and 0.30 mmol . kg-1 . min-1 i.v.). Plasma alpha-amino nitrogen levels increased significantly from 7.1 +/- 0.3 to 13.0 +/- 0.9 and 25.5 +/- 2.1 mg/dl, respectively, in response to the two doses, and GFR increased significantly from 3.2 +/- 0.4 to 4.0 +/- 0.5 and 4.6 +/- 0.5 ml/min, respectively. Arterial pressure did not change. Renal amino acid reabsorption was significantly increased at all time points during the amino acid infusion, reaching a value nearly five times that of control by the last clearance period. Na+ reabsorption was also increased throughout the infusion. Na+, K+, and Cl- excretions increased significantly only at the very last time point. These data indicate that the mechanism or mechanisms responsible for amino acid-induced hyperfiltration are present and functional even before birth in the sheep. Because maternal eating patterns and protein intake are known to change maternal plasma amino acid levels and amino acids are actively transported across the placenta, our findings suggest that both acute and chronic changes in maternal protein intake may alter fetal renal function.

scholarly journals Effect of Intravenous Amino Acid Infusion on Leucine Oxidation Across the Mammary Gland of the Lactating Goat

1996 ◽  
Vol 79 (12) ◽  
pp. 2217-2224 ◽  
Author(s):  
B.J. Bequette ◽  
F.R.C. Backwell ◽  
J.C. MacRae ◽  
G.E. Lobley ◽  
L.A. Crompton ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Amino Acid ◽  
Acid Infusion ◽  
Amino Acid Infusion ◽  
Leucine Oxidation

Effect of hyperinsulinemia on amino acid utilization and oxidation independent of glucose metabolism in the ovine fetus

2006 ◽  
Vol 291 (6) ◽  
pp. E1333-E1340 ◽  
Author(s):  
Laura D. Brown ◽  
William W. Hay
Keyword(s):  
Amino Acid ◽  
Glucose Metabolism ◽  
Oxidation Rate ◽  
Glucose Oxidation ◽  
Glucose Utilization ◽  
Control Period ◽  
Fetal Sheep ◽  
Leucine Oxidation ◽  
Oxidation Rates ◽  
C Value

We studied the effect of acute hyperinsulinemia on amino acid (AA) utilization and oxidation rates independent of insulin-enhanced glucose metabolism in fetal sheep. Metabolic studies were conducted in each fetus ( n = 11) under three experimental periods. After control period (C) study, a fetal hyperinsulinemic-euglycemic-euaminoacidemic (HI-euG-euAA) clamp was established, followed by a hyperinsulinemic-hypoglycemic-euaminoacidemic (HI-hypoG-euAA) clamp to decrease glucose metabolic rates toward C values. Infusions of 3H20, l-[1-13C]leucine, and [14C(U)]glucose were administered to measure blood flow, leucine oxidation, and fetal glucose uptake, utilization, and oxidation in each period. Fetal glucose utilization rate increased 1.7-fold with hyperinsulinemia (C 5.8 ± 0.8 mg·kg−1·min−1, HI-euG-euAA 10 ± 1.3 mg·kg−1·min−1, P < 0.0001), returning to rates not different from C with hypoglycemia (HI-hypoG-euAA 7.1 ± 0.9 mg·kg−1·min−1 vs. C value, P = 0.15). Fetal glucose oxidation rate increased 1.7-fold with hyperinsulinemia (C 3.1 ± 0.2 mg·kg−1·min−1, HI-euG-euAA 5.4 ± 0.4 mg·kg−1·min−1, P < 0.0001) and decreased to near control rates with hypoglycemia (4.0 ± 0.3 HI-hypoG-euAA vs. C value, P = 0.006). AA utilization rates increased with hyperinsulinemia for all essential and most nonessential AAs ( P < 0.001) and did not change when insulin-induced increases in glucose utilization returned to control rates. Leucine oxidation rate increased 1.7-fold with hyperinsulinemia (C 1.0 ± 0.3 μmol·min−1·kg−1, HI-euG-euAA 1.7 ± 0.3 μmol·min−1·kg−1, P < 0.002) and did not change when glucose oxidation rate was decreased with hypoglycemia. These results demonstrate that, in fetal sheep, insulin promotes AA utilization and oxidation independent of its simultaneous effects on glucose metabolism. In acute hyperinsulinemic conditions, AA oxidation does not change when insulin-induced glucose utilization is prevented.

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