PMID- 21508089
OWN - NLM
STAT- MEDLINE
DCOM- 20110728
LR  - 20230318
IS  - 1938-3207 (Electronic)
IS  - 0002-9165 (Linking)
VI  - 93
IP  - 6
DP  - 2011 Jun
TI  - Influence of leucine on protein metabolism, phosphokinase expression, and cell 
      proliferation in human duodenum1,3.
PG  - 1255-62
LID - 10.3945/ajcn.111.013649 [doi]
AB  - BACKGROUND: Although leucine increases protein anabolism through the mammalian 
      target of rapamycin (mTOR) pathway in human muscles, its effects on intestinal 
      mucosal proteins remain unknown. OBJECTIVE: We aimed to assess the effects of 
      leucine on duodenal protein metabolism in healthy humans and to elucidate the 
      signaling pathways involved. DESIGN: Eleven healthy volunteers received for 5 h, 
      on 2 occasions and in random order, an enteral supply of maltodextrins (0.25 g . 
      kg(-1) . h(-1)) or maltodextrins and leucine (0.035 g . kg(-1) . h(-1)) 
      simultaneously with a continuous intravenous infusion of [(2)H(5)]phenylalanine 
      (9 mumol . kg(-1) .h(-1)). Endoscopic duodenal biopsy samples were collected and 
      frozen until analyzed. Phenylalanine enrichment was assessed by gas 
      chromatography-mass spectrometry in duodenal protein and in free intracellular 
      amino acid pools used as precursor to calculate the mucosal fractional synthesis 
      rate (FSR). Proteasome proteolytic activities and phosphokinase expression were 
      assessed by using specific fluorogenic substrates or macroarrays, respectively. 
      RESULTS: Leucine supplementation slightly reduced FSR (mean +/- SEM: 81.3 +/- 6.3%/d) 
      compared with maltodextrins alone (91.7 +/- 8.5%/d; P = 0.0537). In addition, total 
      proteasome activity decreased significantly with leucine (236 +/- 21 compared with 
      400 +/- 58 relative fluorescence units/mug protein; P < 0.05), with no modification 
      of chymotrypsin-like, trypsin-like, caspase-like, or peptidase activities. 
      Leucine did not affect the mTOR pathway but did increase the phosphorylation 
      states of PI3K, Akt, AMPK, p38 MAPK, JNK, GSK-3alpha/beta, STAT3, and STAT5 and 
      increased cyclin D1 mRNA concentrations, which suggested that leucine may enhance 
      cell proliferation. CONCLUSION: Enteral leucine supplementation decreased 
      proteasome activity in duodenal mucosa and enhanced cell proliferation through 
      the PI3K/Akt/GSK-3alpha/beta-catenin pathway. This trial was registered at 
      clinicaltrials.gov as NCT01254110.
FAU - Coeffier, Moise
AU  - Coeffier M
AD  - ADEN EA4311, Institute for Biomedical Research, Rouen University, Rouen, France, 
      Rouen University Hospital, Rouen, France. moise.coeffier@univ-rouen.fr
FAU - Claeyssens, Sophie
AU  - Claeyssens S
FAU - Bensifi, Malik
AU  - Bensifi M
FAU - Lecleire, Stephane
AU  - Lecleire S
FAU - Boukhettala, Nabile
AU  - Boukhettala N
FAU - Maurer, Brigitte
AU  - Maurer B
FAU - Donnadieu, Nathalie
AU  - Donnadieu N
FAU - Lavoinne, Alain
AU  - Lavoinne A
FAU - Cailleux, Anne-Francoise
AU  - Cailleux AF
FAU - Dechelotte, Pierre
AU  - Dechelotte P
LA  - eng
SI  - ClinicalTrials.gov/NCT01254110
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110420
PL  - United States
TA  - Am J Clin Nutr
JT  - The American journal of clinical nutrition
JID - 0376027
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Messenger)
RN  - 47E5O17Y3R (Phenylalanine)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Cell Proliferation/*drug effects
MH  - Dietary Supplements
MH  - Duodenum/*drug effects/metabolism
MH  - Female
MH  - Humans
MH  - Intestinal Mucosa/*drug effects/metabolism
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Leucine/metabolism/*pharmacology
MH  - Male
MH  - Phenylalanine/metabolism
MH  - Phosphorylation/drug effects
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Protein Biosynthesis/*drug effects/physiology
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction/drug effects
MH  - Young Adult
EDAT- 2011/04/22 06:00
MHDA- 2011/07/29 06:00
CRDT- 2011/04/22 06:00
PHST- 2011/04/22 06:00 [entrez]
PHST- 2011/04/22 06:00 [pubmed]
PHST- 2011/07/29 06:00 [medline]
AID - S0002-9165(23)12956-X [pii]
AID - 10.3945/ajcn.111.013649 [doi]
PST - ppublish
SO  - Am J Clin Nutr. 2011 Jun;93(6):1255-62. doi: 10.3945/ajcn.111.013649. Epub 2011 
      Apr 20.