Citrulline Generation Test: What Does It Measure?
arginine
citrulline
glutamine
gut function
test
Journal
JPEN. Journal of parenteral and enteral nutrition
ISSN: 1941-2444
Titre abrégé: JPEN J Parenter Enteral Nutr
Pays: United States
ID NLM: 7804134
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
31
07
2018
revised:
21
08
2018
accepted:
21
09
2018
pubmed:
26
10
2018
medline:
3
10
2020
entrez:
26
10
2018
Statut:
ppublish
Résumé
The citrulline generation test (CGT) has been proposed as a tool to determine gut function. However, the increase in plasma citrulline concentration that follows a bolus dose of alanyl-glutamine may also result from a reduction in citrulline clearance due to competition with glutamine for transport. A swine model was developed, and stable isotope tracers were used to determine the mechanism behind the increase in plasma citrulline that follows a bolus dose of alanyl-glutamine. Plasma concentrations and enrichments were determined, and a non-steady-state model was used to calculate rates of appearance, disappearance, and conversion. The pig model recapitulated the increase in plasma citrulline observed in humans after a dose of alanyl-glutamine. The dipeptide was rapidly hydrolyzed to its constitutive amino acids. Both citrulline plasma concentration and citrulline rate of appearance increased by ≈45% after the bolus dose of alanyl-glutamine. The conversion of citrulline to arginine and the rate of appearance of arginine also increased. Glutamine contributed up to 25% ± 2% of the rate of appearance of citrulline. No changes in the rate of disappearance of citrulline were observed. Our results indicate that a single bolus dose of alanyl-glutamine increases plasma citrulline concentration by increasing citrulline production without any effect on citrulline disposal. Our findings strongly indicate that the CGT assesses the metabolic response of the gut and that CGT can become a useful tool to evaluate gut mass and function.
Sections du résumé
BACKGROUND
The citrulline generation test (CGT) has been proposed as a tool to determine gut function. However, the increase in plasma citrulline concentration that follows a bolus dose of alanyl-glutamine may also result from a reduction in citrulline clearance due to competition with glutamine for transport.
MATERIALS AND METHODS
A swine model was developed, and stable isotope tracers were used to determine the mechanism behind the increase in plasma citrulline that follows a bolus dose of alanyl-glutamine. Plasma concentrations and enrichments were determined, and a non-steady-state model was used to calculate rates of appearance, disappearance, and conversion.
RESULTS
The pig model recapitulated the increase in plasma citrulline observed in humans after a dose of alanyl-glutamine. The dipeptide was rapidly hydrolyzed to its constitutive amino acids. Both citrulline plasma concentration and citrulline rate of appearance increased by ≈45% after the bolus dose of alanyl-glutamine. The conversion of citrulline to arginine and the rate of appearance of arginine also increased. Glutamine contributed up to 25% ± 2% of the rate of appearance of citrulline. No changes in the rate of disappearance of citrulline were observed.
CONCLUSION
Our results indicate that a single bolus dose of alanyl-glutamine increases plasma citrulline concentration by increasing citrulline production without any effect on citrulline disposal. Our findings strongly indicate that the CGT assesses the metabolic response of the gut and that CGT can become a useful tool to evaluate gut mass and function.
Identifiants
pubmed: 30357864
doi: 10.1002/jpen.1462
pmc: PMC6482105
mid: NIHMS990211
doi:
Substances chimiques
Dipeptides
0
Nitrogen Isotopes
0
Glutamine
0RH81L854J
Citrulline
29VT07BGDA
Arginine
94ZLA3W45F
alanylglutamine
U5JDO2770Z
Types de publication
Evaluation Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
726-733Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM108940
Pays : United States
Informations de copyright
© 2018 American Society for Parenteral and Enteral Nutrition.
Références
J Clin Invest. 2000 May;105(9):1217-25
pubmed: 10791996
Gastroenterology. 2000 Dec;119(6):1496-505
pubmed: 11113071
Pediatr Res. 1992 Oct;32(4):472-8
pubmed: 1437402
Am J Clin Nutr. 2006 Jan;83(1):115-23
pubmed: 16400059
Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E683-90
pubmed: 16684848
J Physiol. 2007 Jun 1;581(Pt 2):819-27
pubmed: 17347276
J Nutr. 2007 Jun;137(6 Suppl 2):1621S-1625S
pubmed: 17513438
Am J Gastroenterol. 2007 Dec;102(12):2814-9
pubmed: 17764491
Aliment Pharmacol Ther. 2008 Jun;27(12):1300-10
pubmed: 18331613
Clin Nutr. 2008 Jun;27(3):328-39
pubmed: 18440672
Am J Clin Nutr. 2008 May;87(5):1282-9
pubmed: 18469251
Am J Physiol Endocrinol Metab. 2010 Jul;299(1):E69-79
pubmed: 20407005
J Nutr. 2010 Aug;140(8):1432-7
pubmed: 20573946
JPEN J Parenter Enteral Nutr. 1990 Jul-Aug;14(4 Suppl):137S-146S
pubmed: 2119459
Rapid Commun Mass Spectrom. 2011 May 15;25(9):1291-6
pubmed: 21491530
Biochem Biophys Res Commun. 1990 Oct 15;172(1):143-8
pubmed: 2222463
J Nutr. 2012 Mar;142(3):572-80
pubmed: 22323761
Br J Pharmacol. 1990 Oct;101(2):237-9
pubmed: 2257431
Am J Physiol Endocrinol Metab. 2012 Dec 1;303(11):E1348-53
pubmed: 23074237
Am J Physiol Renal Physiol. 2014 Sep 15;307(6):F660-5
pubmed: 25056350
Curr Opin Clin Nutr Metab Care. 2016 Jan;19(1):62-6
pubmed: 26560519
Amino Acids. 2017 Jan;49(1):161-172
pubmed: 27714515
J Nutr. 2017 Apr;147(4):549-555
pubmed: 28275102
Clin Exp Gastroenterol. 2017 Apr 28;10:75-81
pubmed: 28496350
Am J Physiol Endocrinol Metab. 2017 Aug 1;313(2):E233-E242
pubmed: 28611027
J Am Heart Assoc. 2018 Feb 25;7(5):
pubmed: 29478971
United European Gastroenterol J. 2018 Mar;6(2):181-191
pubmed: 29511548
J Biol Chem. 1974 Aug 25;249(16):5070-9
pubmed: 4605420
JPEN J Parenter Enteral Nutr. 1994 Sep-Oct;18(5):422-6
pubmed: 7815673
Pediatr Res. 1994 Aug;36(2):202-6
pubmed: 7970935
Am J Physiol. 1993 Dec;265(6 Pt 2):H1965-71
pubmed: 8285235
Proc Natl Acad Sci U S A. 1993 Aug 15;90(16):7749-53
pubmed: 8356080
Clin Chem. 1997 Dec;43(12):2397-402
pubmed: 9439460