title: Effects of an enteral glucose supply on protein synthesis, proteolytic pathways, and proteome in human duodenal mucosa.
abstract: BACKGROUND
  Previous studies have shown that the glucose supply reduces postoperative insulin resistance and improves patient outcomes. However, the effects of luminal glucose on intestinal mucosal proteins remain unknown.
  
  
  OBJECTIVE
  We aimed to assess the effects of an enteral glucose supply on protein synthesis, proteolytic pathways, and proteome in human duodenal mucosa.
  
  
  METHODS
  Twenty healthy volunteers received a 5-h enteral infusion of either saline or glucose (0.12 g · kg(-1) · h(-1)). Simultaneously, a continuous intravenous infusion of l-[1-(13)C]leucine (12 μmol · kg(-1) · h(-1)) was maintained until endoscopy. The duodenal mucosal protein fractional synthesis rate (FSR) was calculated from leucine enrichments assessed in protein and free amino acid pools by gas chromatography-mass spectrometry. Cathepsin D, calpains, and chymotrypsin-like proteasome mucosal activities were evaluated by using specific fluorogenic substrates. A 2-dimensional PAGE-based comparative proteomics analysis was also performed on additional duodenal mucosal biopsy samples to identify differentially expressed proteins.
  
  
  RESULTS
  Duodenal mucosal protein FSR and protease activities were not affected by glucose infusion relative to saline. Nevertheless, the comparative proteomics analysis indicated that 10 protein spots were significantly differentially expressed (ie, at least ±1.5-fold modulated; Student's t test, P < 0.05) in response to the glucose infusion relative to saline. Of the 8 proteins identified by mass spectrometry, α-enolase, cytoplasmic aconitate hydratase, and glutathione S-transferase ω-1 were upregulated, whereas epoxide hydrolase 2 was downregulated.
  
  
  CONCLUSIONS
  Enteral glucose supply affected neither duodenal mucosal protein FSR nor activities of mucosal proteases but altered the duodenal mucosal proteome by modulating the expression of several enzymes involved mainly in carbohydrate and xenobiotic metabolism. This trial is registered at clinicaltrials.gov as NCT00213551.
authors.affiliation: ADEN EA, Institute for Biomedical Research, Rouen University Hospital, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Goichon
authors.forename: Moïse
authors.initials: M
authors.lastname: Coëffier
authors.forename: Sophie
authors.initials: S
authors.lastname: Claeyssens
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lecleire
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Cailleux
authors.forename: Christine
authors.initials: C
authors.lastname: Bôle-Feysot
authors.forename: Philippe
authors.initials: P
authors.lastname: Chan
authors.forename: Nathalie
authors.initials: N
authors.lastname: Donnadieu
authors.forename: Eric
authors.initials: E
authors.lastname: Lerebours
authors.forename: Alain
authors.initials: A
authors.lastname: Lavoinne
authors.forename: Olivier
authors.initials: O
authors.lastname: Boyer
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
mesh_terms: D000154:Aconitate Hydratase / Q000378:metabolism; D000328:Adult; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004386:Duodenum / Q000201:enzymology / Q000378:metabolism*; D004750:Enteral Nutrition; D004851:Epoxide Hydrolases / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism*; D007554:Isotopes; D007930:Leucine / Q000378:metabolism; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects*; D020543:Proteome; D013194:Staining and Labeling; D055815:Young Adult
chemical_list: D004040:Dietary Carbohydrates; D007554:Isotopes; D020543:Proteome; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; D010447:Peptide Hydrolases; D010751:Phosphopyruvate Hydratase; D000154:Aconitate Hydratase; D007930:Leucine; D005947:Glucose