PMID- 19940100
OWN - NLM
STAT- MEDLINE
DCOM- 20100423
LR  - 20211203
IS  - 1522-1601 (Electronic)
IS  - 0161-7567 (Linking)
VI  - 108
IP  - 2
DP  - 2010 Feb
TI  - Leucine modulates contraction- and insulin-stimulated glucose transport and 
      upstream signaling events in rat skeletal muscle.
PG  - 274-82
LID - 10.1152/japplphysiol.00420.2009 [doi]
AB  - Leucine has profound effects on glucose metabolism in muscle; however, the 
      effects of leucine on glucose transport in muscle have not been well documented. 
      We investigated the effects of leucine on contraction- and insulin-stimulated 
      glucose transport in isolated rat epitrochlearis muscle in vitro. In the absence 
      of insulin, tetanic contraction increased 3-O-methyl-D-glucose (3-MG) transport 
      and Thr(172) phosphorylation of the catalytic alpha-subunit of 5'-AMP-activated 
      protein kinase (AMPK), a signaling intermediary leading to insulin-independent 
      glucose transport. Leucine (2 mM, 30 min) significantly enhanced 
      contraction-stimulated 3-MG transport and AMPK phosphorylation, accompanied by 
      increased phosphorylation of p70 S6 kinase (p70S6K) Thr(389). The stimulatory 
      effects of leucine on 3-MG transport and AMPK phosphorylation were canceled by 
      STO-609 blockade of Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) or 
      rapamycin blockade of p70S6K. On the other hand, leucine blunted 
      insulin-stimulated 3-MG transport and reduced insulin-stimulated Akt Thr(473) 
      phosphorylation. Leucine increased insulin-stimulated p70S6K Thr(389) 
      phosphorylation and enhanced the inhibitory phosphorylation of the insulin 
      receptor substrate 1 (IRS1) Ser(636/639). Furthermore, the effects of leucine on 
      insulin-stimulated 3-MG transport and IRS phosphorylation were abolished by 
      rapamycin. These results indicate that leucine activates contraction-stimulated 
      glucose transport and inhibits insulin-stimulated glucose transport in skeletal 
      muscle by activating mammalian target of rapamycin (mTOR)/p70S6K signaling. 
      Enhanced increases in contraction-stimulated AMPK Thr(172) phosphorylation and 
      insulin-stimulated IRS1 Ser(636/639) phosphorylation might be responsible for 
      these opposing effects of leucine, respectively.
FAU - Iwanaka, Nobumasa
AU  - Iwanaka N
AD  - Laboratory of Sports and Exercise Medicine, Graduate School of Human and 
      Environmental Studies, Kyoto Univ., Yoshida-nihonmatsu-cho, Sakyo-ku, Kyoto 
      606-8501, Japan.
FAU - Egawa, Tatsuro
AU  - Egawa T
FAU - Satoubu, Nozomi
AU  - Satoubu N
FAU - Karaike, Kouhei
AU  - Karaike K
FAU - Ma, Xiao
AU  - Ma X
FAU - Masuda, Shinya
AU  - Masuda S
FAU - Hayashi, Tatsuya
AU  - Hayashi T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20091125
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, rat)
RN  - 020IUV4N33 (Phosphocreatine)
RN  - 146-72-5 (3-O-Methylglucose)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 9005-79-2 (Glycogen)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Oncogene Protein v-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - GMW67QNF9C (Leucine)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3-O-Methylglucose/metabolism
MH  - AMP-Activated Protein Kinase Kinases
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Biological Transport, Active/drug effects
MH  - Energy Metabolism/drug effects
MH  - Glucose/*metabolism/*physiology
MH  - Glycogen/metabolism
MH  - Hypoglycemic Agents/*pharmacology
MH  - Insulin/*pharmacology
MH  - Insulin Receptor Substrate Proteins/metabolism
MH  - Leucine/*pharmacology
MH  - Male
MH  - Muscle Contraction/drug effects
MH  - Muscle, Skeletal/*drug effects/*metabolism
MH  - Oncogene Protein v-akt/metabolism
MH  - Phosphocreatine/metabolism
MH  - Protein Kinases/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/*drug effects
EDAT- 2009/11/27 06:00
MHDA- 2010/04/24 06:00
CRDT- 2009/11/27 06:00
PHST- 2009/11/27 06:00 [entrez]
PHST- 2009/11/27 06:00 [pubmed]
PHST- 2010/04/24 06:00 [medline]
AID - 00420.2009 [pii]
AID - 10.1152/japplphysiol.00420.2009 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2010 Feb;108(2):274-82. doi: 
      10.1152/japplphysiol.00420.2009. Epub 2009 Nov 25.