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Title
Oral glutamine accelerates healing of the small intestine and
improves outcome after whole
abdominal radiation.
Author
Klimberg VS; Salloum RM; Kasper M; Plumley DA; Dolson DJ; Hautamaki
RD;
Mendenhall WR; Bova FC; Bland KI; Copeland EM 3d; et al
Source
Arch Surg, 1990 Aug, 125:8, 1040-5
Abstract
The healing effects of glutamine given orally for 8 days as a
single amino acid nutrient after
treatment with whole abdominal radiation (10 Gy) were studied.
Rats received
isonitrogenous and isovolumic diets containing 3% glutamine or
3% glycine. Control rats
were not irradiated but were given identical diets. In irradiated
animals, survival was 100%
in animals receiving glutamine compared with 45% in animals receiving
glycine. Glutamine
ingestion diminished bloody diarrhea and the incidence of bowel
perforation. Arterial
glutamine level was higher in animals receiving glutamine in
the diet, as were gut glutamine
extraction (35% +/- 8% vs 12% +/- 7%) and intestinal glutaminase
activity. These metabolic
improvements were associated with a marked increase in villous
height, villous number,
and the number of mitoses per crypt in rats receiving glutamine.
Glutamine was not
beneficial in control nonirradiated animals. The data demonstrated
that provision of oral
glutamine after abdominal radiation supported gut glutamine metabolism,
improved
mucosal morphometrics, and decreased the morbidity and mortality
associated with this
abdominal radiation model.
Title
Cytokine regulation of intestinal glutamine utilization.
Author
Austgen TR; Chen MK; Dudrick PS; Copeland EM; Souba WW
Source
Am J Surg, 1992 Jan, 163:1, 174-9; discussion 179-80
Abstract
The effects of cytokines on intestinal glutamine metabolism were
studied to gain further
insight into the regulation of altered glutamine metabolism that
occurs during severe
infection. One hundred thirteen adult rats were given a single
dose of interleukin-1 (IL-1, 50
micrograms/kg), tumor necrosis factor (TNF, 50 micrograms/kg
or 150 micrograms/kg),
or saline (controls), and flux studies were performed 4 or 12
hours later. Intestinal blood
flow was not different between control and cytokine-treated animals
at either time point. At
the 4-hour time point, arterial glutamine fell by 16% to 21%
in the cytokine-treated animals
(p less than 0.05); at the 12-hour time point, the arterial glutamine
concentration had
returned to normal. Intestinal glutamine extraction decreased
in the animals treated with IL-1
at both time points (4 hours: 13% +/- 1.3% in IL-1 versus 20%
+/- 1.6% in controls, p less
than 0.05; and 12 hours: 9% +/- 2% in IL-1 versus 17% +/- 2%
in controls, p less than
0.05). Consequently, net intestinal glutamine uptake fell in
the animals treated with IL-1 at
both time points (p less than 0.05). Similarly, the activity
of mucosal glutaminase, the
principal enzyme of glutamine hydrolysis in the gut, fell by
50% in the 4-hour study (6.1 +/-
0.6 mumol/h/mg protein in IL-1 versus 9.6 +/- 0.8 mumol/h/mg
protein in controls, p less
than 0.01) and by 40% in the 12-hour study (5.4 +/- 0.5 mumol/h/mg
protein in IL-1 versus
8.8 +/- 0.4 mumol/h/mg protein in controls, p less than 0.05).
Concomitant with the
aforementioned decrease in gut glutamine metabolism was a 25%
incidence of positive
blood cultures for gram-negative organisms in IL-1 treated rats
studied at the 12-hour time
point (p = 0.05 versus controls). In the doses administered and
at the time points studied,
TNF had no effects on the parameters of gut glutamine metabolism
examined. The results
indicate that IL-1 is a potential mediator of the alterations
in gut glutamine metabolism
observed in sepsis and endotoxemia.
Title
Glutamine metabolism after small intestinal resection in humans.
Author
Darmaun D; Messing B; Just B; Rongier M; Desjeux JF
Source
Metabolism, 1991 Jan, 40:1, 42-4
Abstract
Glutamine and leucine kinetics were measured using stable isotopes
in five enterectomized
patients (residual small bowel, 80 +/- 25 cm [mean +/- SE]) who
were in a near normal
nutritional status at distance from surgery. While parameters
of leucine metabolism were
normal, rates of whole body glutamine utilization were reduced
by 20% in the patients. The
data suggest that the small intestine plays a prominent role
in glutamine utilization in vivo in
humans.
Title
Intestinal glutamine metabolism after massive small bowel resection.
Author
Klimberg VS; Souba WW; Salloum RM; Holley DT; Hautamaki RD; Dolson
DJ;
Copeland EM 3d
Source
Am J Surg, 1990 Jan, 159:1, 27-32; discussion 32-3
Abstract
Gut glutamine utilization after massive small bowel resection
was studied to gain further
insight into the alterations and adaptations in intestinal glutamine
metabolism that occur
during the development of post-resectional hyperplasia. After
resection of the middle 60%
of the small intestine in the rat, gut glutamine metabolism was
studied immediately and 1, 2,
and 3 weeks later. Whole gut glutamine extraction was 22% in
sham controls and it acutely
declined to 12% (p less than 0.01) after bowel resection. Extraction
increased to 31% 1
week later (p less than 0.05) and then returned to normal by
week 2. Gut ammonia release
decreased after massive small bowel resection, whereas intestinal
alanine release increased.
The increase in gut glutamine extraction at 1 week occurred at
a time when jejunal and ileal
DNA and protein content were markedly increased (p less than
0.01). Intestinal glutaminase
content declined initially and then increased by the third week
after bowel resection (p less
than 0.01). With time, increases in gut cellularity and glutaminase
content are associated
with gut glutamine utilization in the shortened small bowel that
is equal to that of the intact
unresected intestine.
Title
Is glutamine essential for the maintenance of intestinal function?
A study in the isolated
perfused rat small intestine.
Author
Plauth M; Raible A; Vieillard Baron D; Bauder Gross D; Hartmann
F
Source
Int J Colorectal Dis, 1999 Apr, 14:2, 86-94
Abstract
Glutamine has received considerable interest as a gut-targeted
nutrient due to its proposed
key role in the maintenance of intestinal structure and function.
We used a preparation of
isolated vascularly perfused rat small intestine to investigate
whether glutamine is essential
for the maintenance of intestinal function. When glutamine was
available, arterial glutamine
was extracted at 15 +/- 2%, and net uptake was -89 +/- 5 nmol
min-1 g-1. Nitrogenous
metabolites ammonia, alanine, and citrulline (41 +/- 7, 41 +/-
4, and 11 +/- 2 nmol min-1
g-1, respectively) were released into the venous perfusate, but
only ammonia was also
excreted into the lumen (36 +/- 3 nmol min-1 g-1). In the absence
of exogenous glutamine
alanine release was halved and that of citrulline and ammonia
nullified. Additional inhibition
of glutamine synthetase yielded the same results. In all cases
variables of tissue function
were fully maintained also in the absence of exogenous and/or
endogenous glutamine. The
inhibition of glutaminase/amidotransferase reactions, however,
was accompanied by a
reduction in glutamine consumption and a graded deterioration
in tissue function. In
conclusion, glutamine seems to be dispensable as a metabolic
fuel to be fully oxidized by
the mucosa. However, the inhibition of major glutamine consuming
pathways was
associated with impaired tissue function and viability. Therefore
the role of intestinal
glutamine metabolism seems to be threefold: (a) providing affluent
amounts of nitrogen
precursors for mucosal anabolic pathways to maintain intestinal
structure and function, (b)
feeding the liver with an optimal substrate mix, and (c) providing
citrulline and thereby
arginine for the whole organism.
Title
Effects of glutamine-supplemented diets on immunology of the
gut.
Author
Alverdy JC
Source
JPEN J Parenter Enteral Nutr, 1990 Jul, 14:4 Suppl, 109S-113S
Abstract
Recent research developments have identified the gastrointestinal
tract as the most
metabolically active organ after surgical stress. In addition
to fulfilling its role as an organ of
digestion and absorption, the gut must maintain immunologic function
in order to protect
the host from invading pathogens. Central to the function of
the intestinal immune system is
the expression of secretory IgA, the most abundant immunoglobulin
in external secretions.
The synthesis and expression of IgA in secretions appear to be
sensitive to dietary alteration
and may be impaired after surgical stress. Data are presented
suggesting that maintenance of
gut mass and barrier function to bacteria via dietary manipulation
may be essential to ensure
host survival during critical illness.
Title
Glutamine enhances gut glutathione production.
Author
Cao Y; Feng Z; Hoos A; Klimberg VS
Source
JPEN J Parenter Enteral Nutr, 1998 Jul, 22:4, 224-7
Abstract
BACKGROUND: The gastrointestinal tract is recognized as having
important metabolic
functions. This study examined gut glutathione (GSH) extraction
and the effect of
supplemental oral glutamine (GLN) on gut GSH fractional release.
METHODS: Healthy
female Fisher-344 rats weighing approximately 150 to 200 g were
pair-fed chow and
supplemented by gavage with 1 g/kg/d GLN or an isonitrogenous
amount of Freamine
(McGaw, St. Louis, MO). Rats were sacrificed at 6 weeks. Arterial
and portal blood was
assayed for GLN and GSH content. The gut GLN and GSH extractions
were calculated.
RESULTS: The gut GLN fractional uptake was increased by approximately
50%, and there
was a near threefold increase in gut GSH fractional release in
the GLN-supplemented group.
CONCLUSIONS: The discovery of gut's role as a major producer
of GSH may give
insight into why feeding via the gut rather than by the venous
route is so important.
Supplemental oral GLN further enhances GLN extraction as well
as GSH fractional release
in the gut.
Title
Glutamine enhancement of structure and function in transplanted
small intestine in the rat.
Author
Frankel WL; Zhang W; Afonso J; Klurfeld DM; Don SH; Laitin E;
Deaton D; Furth EE;
Pietra GG; Naji A; et al
Source
JPEN J Parenter Enteral Nutr, 1993 Jan, 17:1, 47-55
Abstract
Total parenteral nutrition is required by all patients in need
of small bowel transplantation.
Untoward side effects of total parenteral nutrition include atrophy
and hypofunction of the
small intestine. Glutamine, the preferred fuel for the enterocyte,
is presumably present in
insufficient amounts in diets given to patients with intestinal
dysfunction. In a rat model of
total parenteral nutrition and small bowel transplantation, this
study investigated the
following: (1) whether glutamine improves graft structure and
function, (2) the optimal
route of glutamine delivery (intravenous vs direct infusion into
the graft), and (3) the effect
of glutamine on ultrastructure of the graft enterocyte. Lewis
rats underwent small bowel
transplantation as a Thiry-Vella graft and received total parenteral
nutrition for 14 days while
assigned to one of four infusion groups: 2% intravenous glutamine;
2% intravenous
isonitrogenous mixture, nonessential amino acids (control); 2%
glutamine into the graft; or
2% nonessential amino acids into the graft (control). Graft mucosal
villous height, villous
surface area, crypt depth, weight, protein, deoxyribonucleic
acid content, glucose absorption,
and enterocyte ultrastructure were then evaluated. Infusion of
glutamine directly into the
graft significantly increased mucosal villous height (p = .045),
surface area (p = .029), and
glucose absorption (p = .004) when compared with controls. Intravenous
glutamine
infusion significantly increased mucosal villous height (p =
.002), surface area (p = .001),
weight (p = .005), and glucose absorption (p = .04) when compared
with controls. Most
enterotrophic and functional benefits of glutamine were not significantly
different between
intravenous infusions and direct administration into the graft.(Abstract
TRUNCATED
AT 250 WORDS)
Title
Elemental diets in the repair of small intestinal damage.
Author
Gardner ML; Earl SD; Wood D
Address
Department of Biomedical Sciences, University of Bradford, West
Yorkshire, United
Kingdom.
Source
Nutrition, 1997 Jul, 13:7-8, 755-9
Abstract
We have investigated the possible benefits of elemental diets,
especially a diet supplemented
with L-glutamine, on maintenance of intestinal absorptive function
in rat small intestine
damaged by 5-fluorouracil. Although a standard rat diet sustained
better body growth in
control rats, each of the elemental diets and the diet containing
intact casein in place of
hydrolyzed casein was beneficial in promoting less body weight
loss during the 3 d after
5-fluorouracil injection. The same significant benefit was seen
in absorptive activity
measured in small intestine in vitro 3 d after the cytotoxic
injury. Glutamine
supplementation, however, did not confer any significant advantages,
although it did cause
significant elevation of muscle glutamine pools. This elevation
was substantially less than
the corresponding increase in muscle glycine content after dietary
supplementation with
glycine.
Title
Glutamine: an essential amino acid for the gut.
Author
van der Hulst RR; von Meyenfeldt MF; Soeters PB
Source
Nutrition, 1996 Nov, 12:11-12 Suppl, S78-81
Abstract
Glutamine is a non-essential amino acid which is produced in
sufficient amount by the
healthy human body. From experimental work it is known that glutamine
is an important
nutrient for rapidly dividing cells such as cells from the immune
system and the gut. During
several conditions a lack of glutamine may occur. This will result
in functional disturbances
of the immune system and/or the gut. Glutamine is produced mainly
by the muscle tissue.
A decrease in muscle mass during nutritional depletion may result
in decreased glutamine
production capacity. Furthermore during critical illness, there
is an increased demand for
glutamine probably as a result of an increased utilization by
the immune system. In addition,
patients receiving standard parenteral nutrition do not receive
glutamine, until recently,
commercial parenteral nutrition did not contain glutamine because
of instability of this
amino acid during prolonged storage. One of the important functions
of the gut is to prevent
migration of bacteria and/or toxins from the gut lumen into the
systemic circulation. A lack
of glutamine may result in deterioration of this intestinal barrier.
Supplementation of
glutamine to certain patients could be essential. The relation
between glutamine and the gut
in several situations (nutritional depletion, critical illness,
parenteral nutrition) is discussed in
this paper. |
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