title: The citrulline generation test: proposal for a new enterocyte function test.
abstract: BACKGROUND
  The amino acid citrulline is mainly produced by enterocytes from conversion of glutamine. As fasting plasma citrulline proved disappointing as a biomarker for enterocyte dysfunction in clinical practice, we propose a citrulline generation test (CGT) to assess enterocyte function.
  
  
  OBJECTIVE
  To assess the feasibility of a CGT in healthy subjects and patients with decreased enterocyte mass.
  
  
  METHODS
  Nineteen healthy subjects, 16 patients with intestinal villous atrophy and nine patients with short bowel syndrome (SBS) were given an oral bolus of 20 g of the dipeptide alanine-glutamine. Subsequent changes in plasma citrulline and other amino acid concentrations were determined using reverse-phase high-performance liquid chromatography.
  
  
  RESULTS
  Following the oral bolus of alanine-glutamine, plasma citrulline concentrations showed a time dependent rise in healthy subjects of 44 +/- 13% (38-55 micromol/L, P < 0.0001). The slope from baseline plasma citrulline to peak concentrations was 0.22 +/- 0.08, 0.13 +/- 0.04 and 0.09 +/- 0.04 micromol/L/min in healthy subjects, patients with coeliac disease (CeD) and refractory CeD, respectively (healthy subjects vs. CeD P < 0.05, healthy subjects vs. refractory CeD P < 0.001). In patients with SBS, the CGT was able to distinguish between non-adapted and adapted SBS by means of the incremental area under the CGT curve till 90 min (iAUC T90). The iAUC T90 was 447 +/- 179 and 1039 +/- 178 micromol/L/min in non-adapted and adapted SBS, respectively (P = 0.04).
  
  
  CONCLUSIONS
  An oral bolus of alanine-glutamine induces a time-dependent rise in plasma citrulline concentration to an extent dependent on the existence of villous atrophy or enterocyte hyperplasia in CeD, and adapted SBS, respectively.
authors.affiliation: Small Bowel Diseases Unit, Department of Gastroenterology and Hepatology, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. jhc.peters@vumc.nl
authors.forename: J H C
authors.initials: JH
authors.lastname: Peters
authors.forename: N J
authors.initials: NJ
authors.lastname: Wierdsma
authors.forename: T
authors.initials: T
authors.lastname: Teerlink
authors.forename: P A M
authors.initials: PA
authors.lastname: van Leeuwen
authors.forename: C J J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: A A
authors.initials: AA
authors.lastname: van Bodegraven
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D002151:Calorimetry; D002446:Celiac Disease / Q000378:metabolism* / Q000628:therapy; D002956:Citrulline / Q000008:administration & dosage / Q000378:metabolism*; D003430:Cross-Sectional Studies; D020895:Enterocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D002956:Citrulline