Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans.

Nair, K. Sreekumaran; Welle, Stephen; Halliday, D.; Campbell, Robert G.

doi:10.1172/jci113570

Cited by 182 publications

(105 citation statements)

References 46 publications

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13] For example, the published values for quadriceps muscle protein synthesis rate in healthy normal subjects are 0.035-0.063% h −1 (SD = 0.009) by Nair et al, 13 0.033-0.064% h −1 (SD = 0.012) by Gibson et al, 1 and 0.036-0.063% h −1 (SD = 0.011) by Nair et al 8 These ranges and standard deviations compare closely with the values reported in the present study (0.023-0.070% h −1 , SD = 0.014) if subject no. 10 is excluded.…”

Section: Resultsmentioning

confidence: 99%

“…Over the last decade, measurement of the rate of skeletal muscle protein synthesis in vivo [1][2][3][4][5][6][7][8][9][10][11] has been achieved by infusing subjects with a stable isotopically labeled amino acid (e.g. (1-13 C)leucine, valine, phenylalanine) and measuring the rate of incorporation of the labeled amino acid into muscle protein.…”

Section: Introductionmentioning

confidence: 99%

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Measurement of muscle protein fractional synthetic rate by capillary gas chromatography/combustion isotope ratio mass spectrometry

Yarasheski

Smith

Rennie

et al. 1992

Biol. Mass Spectrom.

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The measurement of skeletal muscle protein fractional synthetic rate using an infusion of (1-13 C)leucine and measuring the isotopic abundance of the tracer in skeletal muscle protein by preparative gas chromatography (GC)/ninhydrin isotope ratio mass spectrometry (IRMS) is laborious and subject to errors owing to contamination by 12 C. The purpose of this study was to compare muscle ( 13 C)leucine enrichment measured with the conventional preparative GC/ ninhydrin IRMS approach to a new, continuous-flow technique using capillary GC/combustion IRMS. Quadriceps muscles were removed from four Sprague-Dawley rats after each was infused at a different rate with (1-13 C)leucine for 6-8 h. Muscle leucine enrichment (at.% excess) measured by both methods differed by less than 4%, except at low ( 13 C)leucine enrichments (<0.03 at.% excess). In addition, capillary GC/combustion IRMS was used to assess muscle ( 13 C)leucine enrichment and fractional muscle protein synthesis rate in ten normal young men and women infused with (1,2-13 C 2 )leucine for 12-14 h. This approach reduced the variability of the isotope abundance measure and gave estimates of muscle protein synthesis rate (0.050 ± 0.011% h −1 (mean ± SEM); range = 0.023-0.147% h −1 ) that agree with published values determined using the standard analytical approach. The measurement of ( 13 C)leucine enrichment from skeletal muscle protein by capillary GC/combustion IRMS provides a simple, acceptable and practical alternative to preparative GC/ninhydrin IRMS.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Measurement of muscle protein fractional synthetic rate by capillary gas chromatography/combustion isotope ratio mass spectrometry

Yarasheski

Smith

Rennie

et al. 1992

Biol. Mass Spectrom.

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“…However, we cannot exclude that factors other than insulin deficiency per se might have been responsible for the results observed. Insulin withdrawal was associated with a significant increase in the plasma concentration ofcortisol, glucagon, FFA, ketone bodies, and essential amino acids which have been reported to affect leucine and protein metabolism (13,15,56,58,(70)(71)(72)(73)(74)(75). However, in absence of other hormonal inter-actions in vitro, insulin deficiency decreased the rate of albumin gene transcription and, conversely, insulin replacement increased it (28).…”

Section: Discussionmentioning

confidence: 99%

Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans.

Feo¹,

Gaisano²,

Haymond³

1991

J. Clin. Invest.

155

105

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Insulin deficiency decreases tissue protein synthesis, albumin mRNA concentration, and albumin synthesis in rats. In contrast, insulin deficiency does not change, or, paradoxically, increases estimates of whole body protein synthesis in humans.To determine if such estimates of whole body protein synthesis could obscure potential differential effects of insulin on the synthetic rates of individual proteins, we determined whole body protein synthesis and albumin and fibrinogen fractional synthetic rates using 5-h simultaneous infusions of [14Cjleucine and I13C]bicarbonate, in six type 1 diabetics during a continuous i.v.insulin infusion (to maintain euglycemia) and after short-term insulin withdrawal (12±2 h).Insulin withdrawal increased (P < 0.03) whole body proteolysis by 35% and leucine oxidation by -100%, but did not change 3CO2 recovery from NaH13CO3 or estimates of whole body protein synthesis (P = 0.21). Insulin deficiency was associated with a 29% decrease (P < 0.03) in the albumin fractional synthetic rate but a 50% increase (P < 0.03) in that of fibrinogen.These data provide strong evidence that albumin synthesis in humans is an insulin-sensitive process, a conclusion consistent with observations in rats. The increase in fibrinogen synthesis during insulin deficiency most likely reflects an acute phase protein response due to metabolic stress. These data suggest that the absence of changes in whole body protein synthesis after insulin withdrawal is the result ofthe summation of differential effects of insulin deficiency on the synthesis of specific body proteins. (J. Clin. Invest. 1991. 88:833-840.)

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“…Since increased free fatty acid concentrations have been shown to decrease leucine release in the whole body in dogs (32), as well as at the forearm level in humans (33), and increased ketone body concentrations, in particular fl-hydroxybutyrate, have been shown to stimulate whole-body and muscle protein synthesis (34), the decrease of free fatty acid and ketone body concentrations during insulin might have offset a possible stimulating effect of the hormone itself on amino acid deposition within the forearm. This hypothesis needs to be tested in further studies.…”

Section: Discussionmentioning

confidence: 99%

Effects of acute systemic hyperinsulinemia on forearm muscle proteolysis in healthy man.

Tessari¹,

Inchiostro²,

Biolo³

et al. 1991

J. Clin. Invest.

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To investigate the mechanism(s) of insulin-induced suppression of plasma amino acid concentration and release, we studied forearm as well as whole-body leucine and phenylalanine uptake and release during a peripheral insulin infusion in postabsorptive normal subjects using isotope-dilution methods. Before insulin, leucine and phenylalanine release exceeded uptake (P < 0.01 and P < 0.07, respectively). A net output of a-ketoisocaproate (KIC) was also observed. During insulin, arterial plasma leucine, KIC and phenylalanine concentrations decreased (P < 0.05 or less vs. basal), despite ongoing net output of these substrates by the forearm, that persisted after correction for the mean transit time spent through the extracellular muscular space. By the end of insulin, whole-body leucine and phenylalanine concentrations and rate of appearance were decreased (P < 0.01 vs. basal). However, release and uptake of both amino acids by the forearm were not significantly decreased vs. the preinsulin values. These data indicate that systemic hyperinsulinemia acutely decreases plasma amino acid concentrations by acting primarily at sites other than skeletal muscle. (J. Clin. Invest. 1991. 88:27-33.) Key words: amino acid uptake * amino acid release * leucine rate of appearancephenylalanine rate of appearance * net amino acid output Introduction The mechanisms by which insulin influences amino acid as well as protein turnover in vivo have been investigated with isotope dilution techniques in the last years, both in the whole body and at organ level (1-7). While there is a general agreement on the effect ofthe hormone to decrease whole-body rate of appearance (Ra)' of essential amino acids and therefore of

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Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans.

Cited by 182 publications

References 46 publications

Measurement of muscle protein fractional synthetic rate by capillary gas chromatography/combustion isotope ratio mass spectrometry

Measurement of muscle protein fractional synthetic rate by capillary gas chromatography/combustion isotope ratio mass spectrometry

Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans.

Effects of acute systemic hyperinsulinemia on forearm muscle proteolysis in healthy man.

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