Vol. 89, Issue 2, 573-580, August 2000
Duodenal vs. gastric administration of labeled leucine for the
study of splanchnic metabolism in humans
Pascal
Crenn,
Francois
Thuillier,
Benjamin
Rakatoambinina,
Monique
Rongier,
Dominique
Darmaun, and
Bernard
Messing
Institut National de la Santé et de la Recherche
Médicale, U 290, Hôpital Lariboisière-Saint-Lazare,
75010 Paris, France
 |
ABSTRACT |
Low-rate (6 ml/h) intragastric
infusion of stable, isotope-labeled amino acids is commonly used to
assess the splanchnic handling of amino acids in humans. However, when
used in the postabsorptive state, this method yields unreliable plasma
isotopic enrichments, with a coefficient of variation >10%. In this
metabolic condition, we confirmed in six subjects that an intragastric
infusion of L-[2H3]leucine at 6 ml/h yields an unreliable isotopic steady state in plasma amino acids
with a coefficient of variation of 43 ± 12% (mean ± SD).
In five additional subjects, we assessed the effects of 1)
increasing the rate of delivery of a leucine tracer in an isotonic
plasmalike solution at 240 ml/h into the gastric site, and
2) changing the site of infusion from gastric to duodenal with this same high rate of delivery. In contrast to the
gastric route, and regardless of the rate of delivery, only the
intraduodenal route allowed 1) isotopic plasma steady state
(i.e., coefficients of variation were <10%: 5 ± 3%), and
2) reproducible leucine extraction coefficients (22 ± 5%). We conclude that an infusion site that bypasses the gastric
emptying process, i.e., the duodenal route, along with delivery of a
plasmalike solution, is necessary to reach isotopic steady state in
plasma when labeled leucine is infused into the gastrointestinal tract
in the postabsorptive state.
duodenum; stomach; stable isotopes
| |
INTRODUCTION |
THE PRIMED,
CONSTANT INTRAVENOUS (iv) infusion of amino acids labeled with
stable isotopes has become the reference method for studying whole body
protein kinetics in humans (23).
L-[1-13C]leucine is the most commonly used
tracer because it is possible to estimate rates of protein oxidation
from expired breath 13CO2 measurement, whereas
plasma [13C]leucine enrichment at steady state allows for
the calculation of the leucine appearance rate, an index of protein
breakdown. Indeed, during iv infusion, a steady state reflected by a
coefficient of variation [CV = (SD/mean) × 100] <10% in
plasma isotopic enrichment allows for the calculation of the kinetic
parameters of protein metabolism using steady-state equations. The use
of splanchnic catheterization, either in animals or humans, has
demonstrated the important contribution of intestinal and hepatic
tissues to whole body protein metabolism (33,
34). To assess splanchnic amino acid metabolism in a
noninvasive fashion, the constant gastric infusion of a labeled amino
acid has been used in conjunction with the iv infusion of another
tracer of the same amino acid. This dual route of infusion allows the
calculation of "first pass splanchnic extraction," a reflection of
the intestinal and hepatic utilization of the amino acid. With the
assumption that there is no malabsorption of the tracer, which is
unlikely because <1% of radioactivity of
[14C]phenylalanine was found in stools after oral
[14C]phenylalanine administration (5), the
comparison between the plasma enrichments of the enterally and
itravenously infused tracers will allow calculation of the splanchnic
extraction coefficient (f). Nevertheless, there are
difficulties in obtaining isotopic steady state via the gastric route,
as evidenced by a CV >10% for plasma enrichment, especially in the
postabsorptive state. For example, in one study, the CV was 40% with
intragastric (ig) L-[1-13C]leucine
(10), and Hoerr et al. (15) acknowledged that
the variability of plasma enrichment tracer is higher with the ig than
with the iv route. In most studies, an ig tracer infusion route was
chosen, with the exception of two studies, in which duodenal routes of
infusion were used (17, 19). In all but one
of these studies (17), the flow rate of tracer solution infusion was similar to the iv tracer rate (i.e., 6-12
ml/h). When the oral route was chosen, the tracer was administered at 15- (24, 27) or 20-min (5,
6, 30, 31) intervals in a 200-ml
glass of water in the postabsorptive state. The latter mode of oral
tracer administration failed to achieve a satisfactory isotopic steady
state as well, and the authors noted that unreliable plasma enrichment
plateaus were obtained (24).
To 1) obtain reproducible f values and
2) compare different metabolic situations, it is important
to achieve a robust steady state after enteral infusion of tracer. The
aim of the present study was, therefore, to determine whether more
reliable isotopic plateaus, with CVs 
10% (i.e., similar
to those obtained via the iv route), can be achieved in the
postabsorptive state through modifications in the mode of enteral
tracer delivery by either increasing the rate of delivery (240 vs. 6 ml/h) in the gastric site, or by changing the site of infusion from ig
to intraduodenal (id) with this same high rate of delivery. Labeled
leucine, a reference tracer for in vivo protein metabolism study, was used.
| |
METHODS |
Subjects
A total of 11, healthy male volunteers (n = 6, subjects 1-6 in protocol A, ig and iv
administration of tracers; n = 5, subjects 7-11 in protocol B, ig, iv, and id administration
of tracers), without previous metabolic or digestive diseases, ages
21-47 yr [32.0 ± 6.9 (SD) yr] were studied at the
Saint-Lazare Hospital Nutrition Unit. They weighed 67-95 kg
(72.0 ± 11.0 kg) with a height of 163-190 cm (177 ± 6.6 cm). Body mass index was 20.1-26.3 kg/m2
(23.0 ± 2.3 kg/m2). The subjects were told of the
purpose and risks of the study and gave their written consent in
accordance with a protocol approved by the Paris-VII University ethics committee.
Materials
L-[1-13C]leucine (99%
13C),
L-[5,5,5-2H3]leucine (99%
2H3), and NaH13CO3
(99% 13C) were obtained from Tracer Technologies
(Somerville, MA). Before each infusion, sterile solutions of the
tracers were prepared using an aseptic technique. Accurately weighed
amounts of each labeled amino acid were dissolved in a known amount of
sterile, pyrogen-free, 0.9% NaCl solution and filtered through a
0.22-µm filter (Millipore, Bedford, MA) into a sterile bottle that
was then aseptically sealed. Tracer preparations were verified to be
pyrogen free and sterile. Solutions were prepared <16 h before use and
kept at 4°C.
Experimental Design
The protocol designs are depicted in Fig.
1. The night before each infusion, each
subject ate dinner at 2000 and then fasted until the next morning.
Before infusion of the isotopic tracers, which began at 0800, two short
iv catheters were placed, one in a forearm vein for isotope infusion
and the other in a superficial vein of the contralateral hand for blood
sampling. During the sampling periods, the hand was placed in a heated
box (air temperature = 60-65°C) to produce arterialized
venous blood (8). At the beginning of each experiment,
priming doses of NaH13CO3 (0.2 mg/kg), to
saturate the bicarbonate pool, and the equivalents of 1 h of
infusion for each amino acid tracer were injected iv. For the
gastrointestinal experiments of protocol B, the priming doses were given via the gastrointestinal route. In every experiment, the subject's head was placed under the canopy of an indirect calorimeter (MMC-Horizon; Beckman Instruments, Anaheim, CA), allowing continuous measurement of gas flows and carbon dioxide and oxygen pressures (18). Before tracer infusion was started, blood
samples and three expired air samples were obtained for determination of basal, natural abundance of isotopic enrichment in plasma leucine, the 
-ketoacid of leucine (KIC), and breath
13CO2. Gas sampling was performed directly from
the ventilated canopy as previously described (18), and
carbon dioxide production was measured over 20-min periods. Expired air
and arterialized blood samples were collected for the measurement of
steady-state breath 13CO2 and plasma leucine
enrichments, respectively. Each blood sample was immediately
centrifuged at 4°C and frozen at 
20°C until analysis.
Intravenous administration of tracer.
A routine, 4-h priming constant infusion (6 ml/h) of a saline solution
with L-[1-13C]leucine at 4 µmol · kg
1 · h1 was given in
protocols A and B. The tracer was
administered through calibrated syringe pumps (Roucaire Laboratory,
Vélizy-Villacoublay, France), and blood samples were taken every
20 min during the final 2 h of tracer infusion.
Digestive administration of tracers.
To access the gastric and duodenal sites, we used a silicone feeding
tube (3.3 mm or 10-Fr diameter, length = 125 cm; Vygon, Ecouen,
France) that was weighted by 20 g of mercury metal in the duodenal
studies. The position of the feeding tube tip, either in the stomach
antrum or into the duodenum at Treitz's flexure, was controlled by
X-ray just before the beginning of the study, with the tube being fixed
to the nostril to prevent movement. In these digestive experiments,
tracers were infused in an isotonic plasmalike saline solution
(14) (composed of 135 meq/l Na, 5 meq/l K, 110 meq/l Cl,
30 meq/l HCO3; osmolality = 280 mosmol/kgH2O, osmolality was verified before each
infusion). In protocol A (n = 6),
L-[2H3]leucine was administered
by the ig route and simultaneously infused at 6 ml/h with iv
L-[1-13C]leucine. In protocol B
(n = 5), the iv, ig, and id studies were separated
by 1 or 2 wk, in random order. In protocol B, enteral leucine tracer was administered via either the ig or id routes and was
infused at 240 ml/h. In protocol A, the gastric tracer L-[2H3]leucine was administered
at 4 µmol · kg1 · h1 for
4 h. In protocol B, the gastric and duodenal tracer
L-[1-13C]leucine was administered at 6 µmol · kg1 · h1 for 6 h. To obtain a minimum of four data points for better calculation of
the CV, blood samples were taken every 20 min during the ig studies of
protocol A and every 30 min in the ig and id studies of
protocol B.
In addition, after 4 h of iv infusion in three subjects of
protocol A, L-[2-15N]glutamine
(99% 15N; Tracer Technologies) was switched to ig infusion
for 4 h and infused at 6 ml/h at 6 µmol · kg1 · h1. In
three subjects of protocol B,
L-[2-15N]glutamine was separately
administered iv, switched as in protocol A (12 µmol
· kg1 · h1 for 6 h) to the
digestive tract (in the stomach antrum or into the duodenum at
Treitz's flexure), and infused at 240 ml/h in the isotonic
plasmalike solution. Results of splanchnic
L-[2-15N]glutamine metabolism on these
preliminary experiments are presented in the DISCUSSION.
Analytic Methods
Stable isotope enrichments in plasma leucine and KIC were
determined by electron-impact gas chromatography-mass spectrometry (GC-MS; model R1010T, Nermag, Argenteuil, France). Plasma leucine was
analyzed as its N-trifluoroacetyl, n-butyl (TFAB)
derivative and KIC as its quinoxalinol-trimethylsilyl (Q-TMS)
derivative (23). Separate injections were used for leucine
and KIC in the GC-MS. Isothermal programs at 150 and 190°C were used
for TFAB-leucine and Q-TMS-KIC, respectively. Injections were made into
a 0.22 mm × 25 m OVl capillary gas chromatography column
(Spiral, Dijon, France) with a split ratio of 1/25 and helium as a
carrier gas. Ions at mass-to-charge ratios (m/z) of 228 and
227, 185 and 182, and 233 and 232 were selectively monitored to
quantitate the molar ratios of
L-[1-13C]leucine to natural leucine isotope,
L-[2H3]leucine to natural
leucine, and [13C]KIC to natural KIC, respectively.
Plasma glutamine was analyzed as its N-acetyl,
n-propyl (NAP) ester derivative (11).
Isothermal program at 230°C was used for NAP-glutamine. Ions at
m/z 187 and 186 were selectively monitored to quantitate the
molar ratios of L-[2-15N]glutamine to natural
glutamine. Enrichments were calculated from the background-corrected
isotope ratios as previously described (23). The CV of the
analytic method (repeatability, n = 10) was <2% for
L-[1-13C]leucine,
L-[2H3]leucine, and
L-[2-15N]glutamine, and <3% for
[13C]KIC. Analyses of breath
13CO2 were performed by automated gas
chromatography-isotope ratio mass spectrometer (GC-IRMS; Tracer Mass,
Europa Scientific, Crewe, UK).
Calculations
Leucine f (fLeu) was
calculated with plasma enrichment (Ep; mol %excess) after iv and
digestive infusion with normalization by tracer infusion rate
(22)
|
(1)
|
in which Epdig is plasma enrichment after digestive
infusion; idig is digestive tracer infusion rate
(µmol · kg1 · h1);
Epiv is plasma enrichment after iv infusion and
iiv is iv tracer infusion rate.
Leucine splanchnic oxidation (fox) was
calculated according to Matthews et al. (21)
|
(2)
|
in which F13CO2 is
13CO2 flux from [13C]leucine
oxidation
|
(3)
|
in which ECO2 is the 13C
enrichment (mol %excess) in expired carbon dioxide; wt is the
subject's body weight; 
CO2 is total carbon dioxide production in milliliters; 44.6 converts ml
CO2/min to µmol/min; 60 is min/h; r is the estimated
fraction of carbon recovered in expired air [i.e., 0.72 in the fasting
state (15)]; and 100 converts enrichment to fractions of unity.
Statistical Analysis
To test the reliability of plateau enrichments in plasma and in
expired 13CO2, two methods were used:
1) CV of enrichment [(enrichment SD/mean enrichment) × 100], in which a CV 10% was considered consistent with the
existence of a steady state (2, 34), and
2) linear regression analysis of enrichment vs. time, in
which a slope different from zero was considered inconsistent with
steady state. To test for differences in enrichment variances at
plateau between the iv and ig methods in protocol A and the
iv, ig, and id methods in protocol B, a two-way
(subject × method) ANOVA (SPSS 7.5, Chicago, IL) was used. The
significance level for statistical tests was established at
P 0.05.
| |
RESULTS |
Enrichments in iv Experiments
A steady state was observed between 140 and 240 min, with a mean
plasma enrichment CV of 7% (range: 2-13%) for
L-[1-13C]leucine (Fig.
2) and 12% (4-22%) for
[13C]KIC (n = 11, number of
measurements = 5, range 4-6). Linear regression
analysis in every subject showed a nonsignificant correlation of plasma
enrichment vs. time. Intravenous infusion allowed a steady state in
13CO2 breath enrichment (CV = 5%;
1-9% range) to be reached as well.
View larger version (22K):
[in this window]
[in a new window]
|
Fig. 2.
Plasma L-[1-13C]leucine
enrichment during L-[1-13C]leucine
intravenous administration at 6 ml/h.
|
|
Enrichments and Splanchnic Protein Metabolism in Gastric and
Duodenal Experiments
Protocol A: ig administration of leucine tracer at 6 ml/h.
There was no isotopic enrichment steady state for plasma
L-[2H3]leucine enrichment,
because the mean CV was 43% (range = 22-54%, n = 6, number of measurements = 5, range 4-6;
Fig. 3). In subjects 1 and 4, linear regression analysis of plasma
L-[2H3]leucine enrichment vs.
time showed a slope significantly different from zero. Enrichment
variance at plateau was significantly greater after ig
administration than with iv (statistic F = 48.5, P = 0.001) administration. Leucine splanchnic
extraction was 28% yet varied over a wide range (from 26 to 49%;
see Table 1).
Protocol B: ig and id administration of leucine tracer at 240 ml/h.
For gastric infusion (n = 4) there was no steady state
in plasma isotopic enrichment, as the mean CV (number of
measurements = 7, range 7-8) was 33% (range 27-43%)
for L-[1-13C]leucine (Fig.
4A) and 38% (range
24-55%) for KIC. In contrast, isotopic plateaus were
observed in id infusion (n = 4) between 150 and 240 min, extending to 360 min (Fig. 4B), with a mean CV (number
of measurements = 7, range 6-8) at 5% (range 3-9%) and 12% (range 9-19%) for L-[1-13C]leucine
and [13C]KIC, respectively. The ratio of
[13C]KIC to L-[1-13C]leucine
enrichment in plasma was not significantly different between iv, ig,
and id administration (Table 2). Linear
regression analysis of plasma
L-[1-13C]leucine enrichment vs. time showed
that, in ig, subjects 9 and 11 had slopes
significantly different from zero, with a 100% variation of
enrichment, whereas this was not the case in any of the four id
infusion experiments. Enrichment variance at plateau was significantly greater during ig administration than during iv (F = 41.9, P < 0.01) or id (F = 46.7, P < 0.01) administration. No difference was found
between iv and id infusion (F = 2.5, P = 0.21). The mean values for fLeu, calculated
for gastric (fiv/ig) and duodenal infusion
(fiv/id; Table 1), were of the same order of
magnitude, both being 22%. For splanchnic leucine extraction, there
was a large variation between subjects with ig vs. id infusion
(21-54% vs. 14-26%). In contrast, both ig and id infusion
allowed for a steady state in breath
13CO2 enrichment with a CV of 11 and
8%, respectively. During ig infusion, fox
reached negative values in three out of four cases, whereas
fox was 2% after id infusion (range 3 to
6%), with a negative value in only one out of four subjects (Table 1).
View larger version (24K):
[in this window]
[in a new window]
|
Fig. 4.
Plasma L-[1-13C]leucine
enrichment during L-[1-13C]leucine gastric
(A) and duodenal (B) administrations at 240 ml/h.
|
|
| |
DISCUSSION |
The present study demonstrates that, in the
postabsorptive state, infusion of stable isotope-labeled leucine into
the gastrointestinal tract yields a plateau of plasma isotopic
enrichment (i.e., steady state), and a precise and
reproducible determination of f results when the tracer is
infused via the duodenal route. In contrast, the gastric route of
infusion, regardless of the rate of infusion (6 or 240 ml/h), does not
allow steady state to be reached.
The 240 ml/h (4 ml/min) rate was used because it is the known
physiological rate of gastric emptying for nonnutritional solutions (13). Indeed, the kinetics of gastric emptying after
administration of calorie-free liquids depend on volume and osmolarity.
Our data suggest that the high variability of plasma enrichments with
gastric infusion in the postabsorptive state is accounted for by known aspects of digestive physiology. The 6 ml/h rate of administration was
probably too low to ensure a constant rate of gastric emptying for the
tracer solution; therefore, we speculate that the variability of plasma
enrichment in the postabsorptive state is likely due to changes in
absorption kinetics related to changes in gastric emptying and
digestive motility (26, 34). Although neither manometry of gastric tone nor assessment of small bowel motility was
performed in the present study, the infusion of normal saline at a low,
regular rate (5 ml/min) into the stomach is known to be associated with
pulsatile gastric emptying in relation to antropyloric motility
modifications in the pig (20). In humans, the gastric emptying of 50 or 200 ml of a calorie-free liquid is influenced by time
of administration (26), because the cycle of
interdigestive migrating myoelectric complexes ranges from 15 min to
3 h. Phase III of each migrating myoelectric complex increases
gastric emptying during its average 8-min duration. During enteral
feeding, the plasma isotopic enrichment of the ig-infused tracer had a
CV of 15% (11). It can be postulated that this was due to
regular gastric emptying, as observed during continuous enteral
nutrition. The present study demonstrates that the digestive infusion
of stable isotope-labeled leucine should not use the gastric route in
the postabsorptive state, even under optimized conditions chosen to
take gastrointestinal motility into account. The duodenal route of
infusion was chosen because this route bypasses gastric emptying.
The duodenal tube was well tolerated without abdominal discomfort,
vomiting, or diarrhea. We did not attempt to use a low rate of duodenal
infusion because postabsorptive digestive motility would have
compromised tracer absorption, as demonstrated by a variable orocaecal
transit time measured by Di Lorenzo et al. (12) with a
hydrogen breath test after lactulose duodenal low-dose administration
(i.e., 15 g in 10 ml of water). A plasmalike
electrolyte solution was chosen because it mimics the composition of
intestinal fluid at Treitz's flexure, prevents digestive secretion,
and allows absorption of water and electrolytes from intestinal lumen
into portal blood (13). The differences between the
gastric and duodenal routes of tracer infusion are unlikely to reflect
differences in absorption kinetics. If this were the case, results
would differ between amino acids. In fact, preliminary experiments
carried out in three subjects with labeled glutamine tracers (Table
3) revealed, compared with leucine, the
same trend for glutamine, even though the absorption rate constants and
transport mechanisms are different and rely on different transporters
in the small intestine (28). That large and small CVs in
plasma enrichment were observed after ig and id infusion, respectively,
for both leucine and glutamine, suggests that our results are
applicable to amino acids with different f values
(22).
The present study confirms the previously documented f of
22% for L-[1-13C]leucine (15,
21). Nevertheless, splanchnic extraction seems to be
variable in the literature, especially in the postabsorptive state
between subjects (15), as well as between the
postabsorptive state and the fed state (8,
10, 19) or as a function of age
(4). In our study, digestive experiments were extended to
a 6-h duration for two reasons. A delay in the rise in plasma tracer
enrichment was expected because the enterally infused tracer had to
cross multiple membranes on its way through the splanchnic tissues. In
fact, the time needed to reach plateau was the same between iv and id
infusion. Although many of the proteins synthesized in splanchnic
tissues have a fast turnover (21), there was no evidence
of leucine recycling during the course of a 6-h tracer infusion because
there was no rise in enrichment by the end of the experiment in the
studied subjects. Isotopic plateau in expired 13CO2 breath air was comparable for all
experiments. This was expected because of the slow kinetics of
CO2, a "terminal" metabolic product. With f,
we were able to estimate the first pass fox, as
described (22). Calculation of fox
yielded negative values with ig infusion, but, with id infusion, the
mean fox value was 2%, which was close to the
1.9% obtained by others in postabsorptive humans (21) and
similar to the 3.5% determined by catheterization in the dog (34). This suggests that 9% of the tracer extracted by
splanchnic tissues was oxidized in these tissues. Thus it appears that
the splanchnic oxidation of leucine is low, consistent with the view that leucine is not a major fuel for the intestines and liver.
Based on 28 and 5% SDs for fLeu via the ig and
id infusions, respectively, a tentative study designed to detect a 10%
change in leucine splanchnic extraction with a 90% power would have to enroll 165 subjects with the gastric route vs. only 6 subjects with the
duodenal route of tracer delivery. Duodenal tracer infusion should
therefore be suitable for in vivo exploration of splanchnic protein
metabolism in humans in the postabsorptive state, even though
calculation of splanchnic extraction is an indirect method for
assessing splanchnic protein metabolism. The direct method for
assessing in vivo protein intestinal metabolism requires biopsies to
calculate fractional synthetic rate, i.e., the percentage of proteins
synthesized over a given time period in a specific protein or tissue.
For the small intestine, endoscopic biopsies can be performed after
either iv or digestive infusion of tracer. KIC enrichment, a better
predictor of splanchnic tissue leucyl-tRNA enrichment than of plasma
leucine enrichment (3), gives similar results as leucine
for steady state after digestive infusion of tracer. The choice of
tracer infusion route is important to consider because the major source
of amino acids used for protein synthesis in enterocytes
(1) is still controversial (7,
25).
In summary, our results suggest that the use of tracer infusion via the
gastrointestinal tract to explore protein metabolism should ideally
bypass the effect of gastric emptying in the postabsorptive state. To
obtain a reliable steady state in amino acid enrichment, tracer
infusion should be postpyloric. This technique would allow the effects
of fasting and feeding on splanchnic protein metabolism to be reliably
studied. This seems necessary for proper comparisons between healthy
subjects and patients with pathological conditions, for comparisons
between different nutritional regimens, and to study the fractional
rate of protein synthesis in splanchnic tissues, such as small bowel mucosa.
| |
ACKNOWLEDGEMENTS |
This work was supported, in part, by a 1994-AJINOMOTO-Fellowship
grant from the European Society of Parenteral and Enteral Nutrition (to
P. Crenn).
| |
FOOTNOTES |
Address for reprint requests and other correspondence:
B. Messing, Hôpital Lariboisière, 2 rue Ambroise
Paré, 75475 Paris, France (E-mail:
bernard.messing{at}lrb.ap-hop-paris.fr).
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Received 30 June 1999; accepted in final form 20 March 2000.
| |
REFERENCES |
1.
Alpers, DH.
Protein synthesis in intestinal mucosa: the effect of route of administration of precursor amino acids.
J Clin Invest
51:
167-173,
1972.
2.
Armitage, P,
and
Berry G.
Statistical Methods in Medical Research (2nd ed.). Oxford: Blackwell Scientific Editions, 1987.
3.
Baumann, PQ,
Stirewalt WS,
O'Rourke BD,
Howard D,
and
Nair KS.
Precursor pools of protein synthesis: a stable isotope study in a swine model.
Am J Physiol Endocrinol Metab
267:
E203-E209,
1994[Abstract/Free Full Text].
4.
Beaufrère, B,
Fournier V,
Salle B,
and
Putet G.
Leucine kinetics in fed low-birth-weight infants: importance of splanchnic tissues.
Am J Physiol Endocrinol Metab
263:
E214-E220,
1992[Abstract/Free Full Text].
5.
Biolo, G,
Tessari P,
Inchiostro S,
Bruttomesso D,
Fongher C,
Sabadin L,
Fratton MG,
Valerio A,
and
Tiengo A.
Leucine and phenylalanine kinetics during mixed meal ingestion: a multiple tracer approach.
Am J Physiol Endocrinol Metab
262:
E455-E463,
1992[Abstract/Free Full Text].
6.
Biolo, G,
Tessari P,
Inchiostro S,
Bruttomesso D,
Sabadin L,
Fongher C,
Panebianco G,
Fratton MG,
and
Tiengo A.
Fasting and postmeal phenylalanine metabolism in mild type 2 diabetes.
Am J Physiol Endocrinol Metab
263:
E877-E883,
1992.
7.
Bouteloup-Demange, C,
Boirie Y,
Dechelotte P,
Gachon P,
and
Beaufrère B.
Gut mucosal protein synthesis in fed and fasted humans.
Am J Physiol Endocrinol Metab
274:
E541-E546,
1998[Abstract/Free Full Text].
8.
Castillo, L,
Chapman TE,
Yu YM,
Ajami A,
Burke JF,
and
Young VR.
Dietary arginine uptake by the splanchnic region in adult humans.
Am J Physiol Endocrinol Metab
265:
E532-E539,
1993[Abstract/Free Full Text].
9.
Copeland, KC,
Kenney FA,
and
Nair KS.
Heated dorsal hand vein sampling for metabolic studies: a reappraisal.
Am J Physiol Endocrinol Metab
263:
E1010-E1014,
1992[Abstract/Free Full Text].
10.
Cortiella, J,
Matthews DE,
Hoerr RA,
Bier DM,
and
Young VR.
Leucine kinetics at graded intakes in young men: quantitative fate of dietary leucine.
Am J Clin Nutr
48:
998-1009,
1988[Abstract/Free Full Text].
11.
Darmaun, D,
Froguel P,
Rongier M,
and
Robert JJ.
Amino acid exchange between plasma and erythrocytes in vivo in humans.
J Appl Physiol
67:
2383-2388,
1989[Abstract/Free Full Text].
12.
Di Lorenzo, C,
Dooley CP,
and
Valenzuela JE.
Role of fasting gastrointestinal motility in the variability of gastrointestinal transit time assessed by hydrogen breath test.
Gut
32:
1127-1130,
1991[Abstract/Free Full Text].
13.
Emonts, P,
Vidon N,
Bernier JJ,
and
Rambaud JC.
Etude sur 24 heures des flux liquidiens intestinaux chez l'homme normal par la technique de la perfusion lente d'un marqueur non absorbable.
Gastroenterol Clin Biol
3:
139-146,
1979[ISI][Medline].
14.
Fordtran, JS,
Rector FC,
Locklear TW,
and
Ewton MF.
Water and solute movement in the small intestine of patients with sprue.
J Clin Invest
46:
287-298,
1967.
15.
Hoerr, RA,
Matthews DE,
Bier DM,
and
Young VR.
Leucine kinetics from [2H3]- and [13C]leucine infused simultaneously by gut and vein.
Am J Physiol Endocrinol Metab
260:
E111-E117,
1991[Abstract/Free Full Text].
16.
Hoerr, RA,
Yu YM,
Wagner DA,
Burke JF,
and
Young VR.
Recovery of 13C in breath from NaH13CO3 infused by gut and vein: effect of feeding.
Am J Physiol Endocrinol Metab
257:
E426-E438,
1989[Abstract/Free Full Text].
17.
Horber, FF,
and
Haymond MW.
Human growth hormone prevents the protein catabolic side effects of prednisone in humans.
J Clin Invest
86:
265-272,
1990.
18.
Just, B,
Darmaun D,
Koziet J,
Rongier M,
and
Messing B.
Use of a ventilated canopy for assessment of [13C]leucine oxidation in patients receiving total parenteral nutrition.
JPEN J Parenter Enteral Nutr
15:
65-70,
1991[Abstract].
19.
Krempf, M,
Hoerr R,
Pelletier VA,
Marks LM,
Gleason R,
and
Young VR.
An isotopic study of the effects of dietary carbohydrate on the metabolic fate of dietary leucine and phenylalanine.
Am J Clin Nutr
57:
161-169,
1993[Abstract/Free Full Text].
20.
Malbert, CH,
and
Mathis C.
Antropyloric modulation of transpyloric flow of liquids in pigs.
Gastroenterology
107:
37-46,
1994[ISI][Medline].
21.
Matthews, DE,
Marano MA,
and
Campbell RG.
Splanchnic bed utilization of leucine and phenylanine in humans.
Am J Physiol Endocrinol Metab
264:
E109-E118,
1993[Abstract/Free Full Text].
22.
Matthews, DE,
Marano MA,
and
Campbell RG.
Splanchnic bed utilization of glutamine and glutamic acid in humans.
Am J Physiol Endocrinol Metab
264:
E848-E854,
1993[Abstract/Free Full Text].
23.
Matthews, DE,
Motil DK,
Rohrbaugh DK,
Burke JF,
Young VR,
and
Bier DM.
Measurement of leucine metabolism in man from a primed, continuous infusion of L-[1-13C]leucine.
Am J Physiol Endocrinol Metab
238:
E473-E479,
1980[Abstract/Free Full Text].
24.
Melville, S,
McNurlan MA,
McHardy KC,
Broom J,
Milne E,
Calder AG,
and
Garlick PJ.
The role of degradation in the acute control of protein balance in adult man: failure of feeding to stimulate protein synthesis as assessed by L-[1-13C]leucine infusion.
Metabolism
38:
248-255,
1989[ISI][Medline].
25.
Nakshabendi, IM,
Obeidat W,
Russell RI,
Downie S,
Smith K,
and
Rennie MJ.
Gut mucosal protein synthesis measured using intravenous and intragastric delivery of stable tracer amino acids.
Am J Physiol Endocrinol Metab
269:
E996-E999,
1995[Abstract/Free Full Text].
26.
Oberle, RL,
Chen TS,
Lloyd C,
Barnett JL,
Owyang C,
Meyer J,
and
Amidon GL.
The influence of the interdigestive migrating myoelectric complex on the gastric emptying of liquids.
Gastroenterology
99:
1275-1282,
1990[ISI][Medline].
27.
Pelletier, V,
Marks L,
Wagner DA,
Hoerr RA,
and
Young VR.
Branched-chain amino acid interactions with reference to amino acid requirements in adult men: leucine metabolism at different valine and isoleucine intakes.
Am J Clin Nutr
54:
402-407,
1991[Abstract/Free Full Text].
28.
Said, HM,
Van Voorhis K,
Ghishan FK,
Abumurad N,
Nylander W,
and
Redha R.
Transport characteristics of glutamine in human intestinal brush-border membrane vesicles.
Am J Physiol Gastrointest Liver Physiol
256:
G240-G245,
1989[Abstract/Free Full Text].
29.
Schindlbeck, NE,
Heinrich C,
and
Muller-Lissner SA.
Relation between fasting antroduodenal motility and transpyloric fluid movements.
Am J Physiol Gastrointest Liver Physiol
257:
G198-G201,
1989[Abstract/Free Full Text].
30.
Tessari, P,
Inchiosto S,
Barazzoni R,
Zanetti M,
Orlando R,
Biolo G,
Sergi G,
Pino A,
and
Tiengo A.
Fasting and postprandial phenylalanine and leucine kinetics in liver cirrhosis.
Am J Physiol Endocrinol Metab
267:
E140-E149,
1994[Abstract/Free Full Text].
31.
Tessari, P,
Pehling G,
Nissen SL,
Gerich JE,
Service FJ,
Rizza RA,
and
Haymond MW.
Regulation of whole-body leucine metabolism with insulin during mixed-meal absorption in normal and diabetic human.
Diabetes
37:
512-519,
1988[Abstract].
32.
Tessari, P,
Tsalikian E,
Schwenk WF,
Nissen SL,
and
Haymond MW.
Effects of [15N]leucine infused at low rates on leucine metabolism in humans.
Am J Physiol Endocrinol Metab
249:
E121-E130,
1985[Abstract/Free Full Text].
33.
Wahren, J,
Felig P,
and
Hagenfeldt L.
Effect of protein ingestion on splanchnic and leg metabolism in normal man and in patients with diabetes mellitus.
J Clin Invest
57:
987-999,
1976.
34.
Yu, YM,
Wagner DA,
Tredget EE,
Walaszewski JA,
Burke JF,
and
Young VR.
Quantitative role of splanchnic region in leucine metabolism: L-[1-13C,15N]leucine and substrate balance studies.
Am J Physiol Endocrinol Metab
259:
E36-E51,
1990[Abstract/Free Full Text].
J APPL PHYSIOL 89(2):573-580
8750-7587/00 $5.00
Copyright © 2000 the American Physiological Society
TOP
ABSTRACT
INTRODUCTION
