Plasma reciprocal pool specific activity predicts that of intracellular free leucine for protein synthesis

Horber, Fritz F.; Horber-Feyder, C. M.; Krayer, S.; Schwenk, W.; Haymond, Morey W.

doi:10.1152/ajpendo.1989.257.3.e385

Cited by 74 publications

(63 citation statements)

References 42 publications

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“…The LRa and Lox were calculated as described previously (21). a-Ketoisocaproic acid (KIC) is formed when leucine undergoes transamination and is used as a surrogate marker of leucine as it more accurately reflects the intracellular environment (22).…”

Section: Methodsmentioning

confidence: 99%

Oral low-dose testosterone administration induces whole-body protein anabolism in postmenopausal women: a novel liver-targeted therapy

Birzniece

Umpleby

Poljak

et al. 2013

European Journal of Endocrinology

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Objective: In hypopituitary men, oral delivery of unesterified testosterone in doses that result in a solely hepatic androgen effect enhances protein anabolism during GH treatment. In this study, we aimed to determine whether liver-targeted androgen supplementation induces protein anabolism in GH-replete normal women. Design: Eight healthy postmenopausal women received 2-week treatment with oral testosterone at a dose of 40 mg/day (crystalline testosterone USP). This dose increases portal concentrations of testosterone, exerting androgenic effects on the liver without a spillover into the systemic circulation. Outcome measures: The outcome measures were whole-body leucine turnover, from which leucine rate of appearance (LRa, an index of protein breakdown) and leucine oxidation (Lox, a measure of irreversible protein loss) were estimated, energy expenditure and substrate utilization. We measured the concentration of liver transaminases as well as of testosterone, SHBG and IGF1. Results: Testosterone treatment significantly reduced LRa by 7.1G2.5% and Lox by 14.6G4.5% (P!0.05). The concentration of liver transaminases did not change significantly, while that of serum SHBG fell within the normal range by 16.8G4.0% and that of IGF1 increased by 18.4G7.7% (P!0.05). The concentration of peripheral testosterone increased from 0.4G0.1 to 1.1G0.2 nmol/l (P!0.05), without exceeding the upper normal limit. There was no change in energy expenditure and fat and carbohydrate utilization. Conclusions: Hepatic exposure to unesterified testosterone by oral delivery stimulates protein anabolism by reducing protein breakdown and oxidation without inducing systemic androgen excess in women. We conclude that a small oral dose of unesterified testosterone holds promise as a simple novel treatment of protein catabolism and muscle wasting.

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Section: Methodsmentioning

confidence: 99%

Oral low-dose testosterone administration induces whole-body protein anabolism in postmenopausal women: a novel liver-targeted therapy

Birzniece

Umpleby

Poljak

et al. 2013

European Journal of Endocrinology

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“…Leucine rate ofappearance (equalling disappearance) was calculated using the primary pool model by dividing the isotope infusion rate with the plasma [13C -leucine MPE and subtracting the tracer infusion rate (22). The metabolic clearance rates of IGF-I and insulin were the ratios of their infusion rates and their increases in plasma concentrations at the end ofthe studies.…”

Section: Methodsmentioning

confidence: 99%

Comparison of the effects of recombinant human insulin-like growth factor-I and insulin on glucose and leucine kinetics in humans.

Laager¹,

Ninnis²,

Keller³

1993

J. Clin. Invest.

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To compare the metabolic effects of elevated plasma concentrations of IGF-I and insulin, overnight-fasted normal subjects were studied twice, once receiving IGF-I and once insulin at doses that resulted in identical increases in glucose uptake during 8-h euglycemic clamping. Recombinant human IGF-I or insulin were infused in one group at high doses (30 l.g/kg per h IGF-I or 0.23 nmol/kg per h insulin) and in another group at low doses (5 gg/kg per h IGF-I or 0.04 nmol/kg per h insulin). Glucose rate of disappearance (measured by 16,6-D21-glucose infusions) increased from baseline by 239±16% during high dose IGF-I vs 197±18% during insulin (P = 0.021 vs IGF-I). Hepatic glucose production decreased by 37±6% during high dose IGF-I vs 89±13% during insulin (P = 0.0028 vs IGF-I). IGF-I suppressed whole body leucine flux (1-1'3C1-leucine infusion technique) more than insulin (42±4 vs 32±3% during high doses, P = 0.0082). Leucine oxidation rate decreased during high dose IGF-I more than during insulin (55±4 vs 32±6%, P = 0.0001). The decreases of plasma concentrations of free fatty acids, acetoacetate, and f8-hydroxybutyrate after 8 h of IGF-I and insulin administration were similar. Plasma C-peptide levels decreased by 57±4% during high doses of IGF-I vs 36±6% during insulin (P = 0.005 vs IGF-I). The present data demonstrate that, compared to insulin, an acute increase in plasma IGF-I levels results in preferential enhancement of peripheral glucose utilization, diminished suppression of hepatic glucose production, augmented decrease of whole body protein breakdown (leucine flux), and of irreversible leucine catabolism but in similar antilipolytic effects. The data suggest that insulin-like effects of IGF-I in humans are mediated in part via IGF-I receptors and in part via insulin receptors. (J. Clin. Invest. 1993. 92:1903-1909

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“…Desmopressin 4 µg iv Hypoosmolality study 200 C]ketoisocaproate (a-KIC) tracer-to-tracee ratio according to the reciprocal pool model (Cobelli et al, 1987;Horber et al, 1989). Leucine oxidation rate was calculated by dividing the product of 13 CO 2 atom percent excess and CO 2 production rate in expired air by plasma a-[1-…”

Section: Desmopressin 4 µG IVmentioning

confidence: 99%

Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health

Keller¹,

Szinnai

Bilz³

et al. 2003

Eur J Clin Nutr

103

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Alterations of cell volume induced by changes of extracellular osmolality have been reported to regulate intracellular metabolic pathways. Hypo-osmotic cell swelling counteracts proteolysis and glycogen breakdown in the liver, whereas hyperosmotic cell shrinkage promotes protein breakdown, glycolysis and glycogenolysis. To investigate the effect of acute changes of extracellular osmolality on whole-body protein, glucose and lipid metabolism in vivo, we studied 10 male subjects during three conditions: (i) hyperosmolality was induced by fluid restriction and intravenous infusion of hypertonic NaCl (2-5%, wt/vol) during 17 h; (ii) hypo-osmolality was produced by intravenous administration of desmopressin, liberal water drinking and infusion of hypotonic saline (0.4%); and (iii) the iso-osmolality study comprised oral water intake ad libitum. Plasma osmolality increased from 28571 to 29671 mosm/kg (Po0.001during hyperosmolality, and decreased from 28671 to 26571 mosm/kg during hypo-osmolality (Po0.001). Total body leucine flux ([1-13 C]leucine infusion technique), reflecting whole-body protein breakdown, as well as whole-body leucine oxidation rate (irreversible loss of amino acids) decreased significantly during hypo-osmolality. The glucose metabolic clearance rate during hyperinsulinaemic-euglycemic clamping increased significantly less during hypo-osmolality than iso-osmolality, indicating diminished peripheral insulin sensitivity. Glycerol turnover (2-[ 13 C]glycerol infusion technique), reflecting whole-body lipolysis, increased significantly during hypo-osmolar conditions. The results demonstrate that the metabolic adaptation to acute hypo-osmolality resembles that of acute fasting, that is, it results in protein sparing associated with increased lipolysis, ketogenesis and lipid oxidation and impaired insulin sensitivity of glucose metabolism.

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Plasma reciprocal pool specific activity predicts that of intracellular free leucine for protein synthesis

Cited by 74 publications

References 42 publications

Oral low-dose testosterone administration induces whole-body protein anabolism in postmenopausal women: a novel liver-targeted therapy

Oral low-dose testosterone administration induces whole-body protein anabolism in postmenopausal women: a novel liver-targeted therapy

Comparison of the effects of recombinant human insulin-like growth factor-I and insulin on glucose and leucine kinetics in humans.

Effects of changes in hydration on protein, glucose and lipid metabolism in man: impact on health

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