title: Enteral delivery of proteins stimulates protein synthesis in human duodenal mucosa in the fed state through a mammalian target of rapamycin-independent pathway.
abstract: BACKGROUND
  Glutamine modulates duodenal protein metabolism in fasted healthy humans, but its effects in a fed state remain unknown.
  
  
  OBJECTIVE
  We aimed to assess the effects of either glutamine or an isonitrogenous protein mixture on duodenal protein metabolism in humans in the fed state.
  
  
  METHODS
  Twenty-four healthy volunteers were randomly included in 2 groups. Each volunteer was studied on 2 occasions in a random order and received, during 5 h, either an enteral infusion of maltodextrins alone (0.25 g · kg⁻¹ · h⁻¹; both groups) that mimicked a carbohydrate fed state or maltodextrins with glutamine (group 1) or an isonitrogenous (22.4 mg N · kg⁻¹ · h⁻¹) protein powder (group 2). Simultaneously, a continuous intravenous infusion of ¹³C-leucine and ²H₅-phenylalanine (both 9 μmol · kg⁻¹ · h⁻¹) was performed. Endoscopic duodenal biopsies were taken. Leucine and phenylalanine enrichments were assessed by using gas chromatography-mass spectrometry in duodenal proteins and the intracellular free amino acids pool to calculate the mucosal fractional synthesis rate (FSR). Proteasome proteolytic activities and phosphokinase expression were assessed by using specific fluorogenic substrates and macroarrays, respectively.
  
  
  RESULTS
  The FSR and proteasome activity were not different after the glutamine supply compared with after maltodextrins alone. In contrast, the FSR increased (1.7-fold increase; P < 0.05) after protein-powder delivery without modification of total proteasome activity. The protein powder increased insulinemia, PI3 kinase, and erk phosphorylation but did not affect the mammalian target of rapamycin (mTOR) pathway and mitogen-activated protein kinase signal-integrating kinase 1 phosphorylation. A trend for an increase of eukaryotic translation initiation factor 4E phosphorylation was observed (P = 0.07).
  
  
  CONCLUSIONS
  In the carbohydrate fed state, enteral proteins but not glutamine increased duodenal protein synthesis through an mTOR independent pathway in humans.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) Unit 1073, Rouen University Hospital, Rouen, France.
authors.forename: Moïse
authors.initials: M
authors.lastname: Coëffier
authors.forename: Sophie
authors.initials: S
authors.lastname: Claeyssens
authors.forename: Christine
authors.initials: C
authors.lastname: Bôle-Feysot
authors.forename: Charlène
authors.initials: C
authors.lastname: Guérin
authors.forename: Brigitte
authors.initials: B
authors.lastname: Maurer
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lecleire
authors.forename: Alain
authors.initials: A
authors.lastname: Lavoinne
authors.forename: Nathalie
authors.initials: N
authors.lastname: Donnadieu
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Cailleux
authors.forename: Pierre
authors.initials: P
authors.lastname: Déchelotte
mesh_terms: D000328:Adult; D002247:Carbon Isotopes; D003903:Deuterium; D004044:Dietary Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000378:metabolism; D004386:Duodenum / Q000201:enzymology / Q000378:metabolism*; D004750:Enteral Nutrition; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005973:Glutamine / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008297:Male; D010649:Phenylalanine / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D019518:Postprandial Period; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D002247:Carbon Isotopes; D004044:Dietary Proteins; D005973:Glutamine; D010649:Phenylalanine; D003903:Deuterium; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D007930:Leucine