PMID- 18342407
OWN - NLM
STAT- MEDLINE
DCOM- 20080819
LR  - 20220227
IS  - 1532-1983 (Electronic)
IS  - 0261-5614 (Print)
IS  - 0261-5614 (Linking)
VI  - 27
IP  - 3
DP  - 2008 Jun
TI  - Amino acids are necessary for the insulin-induced activation of mTOR/S6K1 
      signaling and protein synthesis in healthy and insulin resistant human skeletal 
      muscle.
PG  - 447-56
LID - 10.1016/j.clnu.2008.01.012 [doi]
AB  - BACKGROUND: Amino acids (AA) activate the mammalian target of rapamycin (mTOR) 
      signaling pathway but overactivation has a negative feedback effect on insulin 
      signaling which may lead to insulin resistance and type 2 diabetes (T2DM). 
      PURPOSE: To determine the effect of reduced AA concentrations on mTOR and insulin 
      signaling during increased nutrient and insulin availability. METHODS: Six 
      control and six T2DM subjects were studied at baseline and following a 5h AA 
      lowering high energy and insulin clamp. Stable isotopic techniques in combination 
      with femoral catheterizations were used to measure AA kinetics across the leg 
      while muscle biopsies were used to measure mTOR and insulin signaling proteins 
      using immunoblotting techniques. RESULTS: AA concentrations decreased by 
      approximately 30-60% in both groups (p<0.05). Phospho-mTOR, S6K1, eEF2, and 
      eIF2alpha were unchanged in both groups following the clamp (p>0.05). In T2DM 
      subjects, IRS-1 serine phosphorylation was unchanged while phospho-AMPKalpha 
      decreased and phospho-Akt, phospho-AS160 and glucose uptake increased following 
      the clamp (p<0.05). In comparison, AA concentrations were maintained in a 
      separate group during an insulin infusion. In this group, phospho-Akt, mTOR and 
      S6K1 (n=4) increased. CONCLUSION: Amino acids are necessary for insulin-induced 
      activation of mTOR signaling and protein synthesis in both healthy and insulin 
      resistant skeletal muscle.
FAU - Drummond, Micah J
AU  - Drummond MJ
AD  - Departments of Physical Therapy, University of Texas Medical Branch, Galveston, 
      TX, USA.
FAU - Bell, Jill A
AU  - Bell JA
FAU - Fujita, Satoshi
AU  - Fujita S
FAU - Dreyer, Hans C
AU  - Dreyer HC
FAU - Glynn, Erin L
AU  - Glynn EL
FAU - Volpi, Elena
AU  - Volpi E
FAU - Rasmussen, Blake B
AU  - Rasmussen BB
LA  - eng
GR  - S10 RR16650/RR/NCRR NIH HHS/United States
GR  - M01-RR-43/RR/NCRR NIH HHS/United States
GR  - K12 HD055929/HD/NICHD NIH HHS/United States
GR  - R01 AR049877/AR/NIAMS NIH HHS/United States
GR  - R01 AR049877-04/AR/NIAMS NIH HHS/United States
GR  - P30 AG024832/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20080314
PL  - England
TA  - Clin Nutr
JT  - Clinical nutrition (Edinburgh, Scotland)
JID - 8309603
RN  - 0 (Amino Acids)
RN  - 0 (Insulin)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Amino Acids/blood/*metabolism
MH  - Case-Control Studies
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Female
MH  - Glucose Clamp Technique
MH  - Humans
MH  - Insulin/metabolism
MH  - *Insulin Resistance
MH  - Male
MH  - Muscle, Skeletal/*metabolism
MH  - Protein Biosynthesis
MH  - Protein Kinases/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
PMC - PMC2484120
MID - NIHMS57855
EDAT- 2008/03/18 09:00
MHDA- 2008/08/20 09:00
PMCR- 2009/06/01
CRDT- 2008/03/18 09:00
PHST- 2007/08/17 00:00 [received]
PHST- 2008/01/17 00:00 [revised]
PHST- 2008/01/25 00:00 [accepted]
PHST- 2008/03/18 09:00 [pubmed]
PHST- 2008/08/20 09:00 [medline]
PHST- 2008/03/18 09:00 [entrez]
PHST- 2009/06/01 00:00 [pmc-release]
AID - S0261-5614(08)00034-4 [pii]
AID - 10.1016/j.clnu.2008.01.012 [doi]
PST - ppublish
SO  - Clin Nutr. 2008 Jun;27(3):447-56. doi: 10.1016/j.clnu.2008.01.012. Epub 2008 Mar 
      14.