PMID- 14651987
OWN - NLM
STAT- MEDLINE
DCOM- 20040318
LR  - 20220408
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 312
IP  - 4
DP  - 2003 Dec 26
TI  - Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose 
      uptake in C2C12 myotubes.
PG  - 1111-7
AB  - To examine which branched-chain amino acids affect the plasma glucose levels, we 
      investigated the effects of leucine, isoleucine, and valine (0.3 g/kg body weight 
      p.o.) in normal rats using the oral glucose tolerance test (OGTT, 2 g/kg). A 
      single oral administration of isoleucine significantly reduced plasma glucose 
      levels 30 and 60 min after the glucose bolus, whereas administration of leucine 
      and valine did not produce a significant decrease. Oral administration of valine 
      significantly enhanced the plasma glucose level at 30 min after the glucose 
      administration and leucine had a similar effect at 120 min. At each measurement 
      timepoint, the insulin levels of the treated groups were lower than that of the 
      control group. We then investigated the effects of leucine, isoleucine or valine 
      at the same concentration (1 mM) on glucose metabolism in C(2)C(12) myotubes in 
      the absence of insulin. Glucose consumption was elevated by 16.8% in the presence 
      of 1 mM isoleucine compared with the control. Conversely, 1 mM leucine or valine 
      caused no significant changes in glucose consumption in the C(2)C(12) myotubes. 
      The 2-deoxyglucose uptake of C(2)C(12) myotubes significantly increased upon 
      exposure to 1-10 mM isoleucine and 5-10 mM leucine. However, isoleucine caused no 
      significant difference in glycogen synthesis in C(2)C(12) myotubes, although 
      leucine and valine caused a significant increase in intracellular glycogen 
      compared with the control. The isoleucine effect on glucose uptake was mediated 
      by phosphatidylinositol 3-kinase (PI3K), but was independent of mammalian target 
      of rapamycin (mTOR). These results suggest that isoleucine stimulates the 
      insulin-independent glucose uptake in skeletal muscle cells, which may contribute 
      to the plasma glucose-lowering effect of isoleucine in normal rats.
FAU - Doi, Masako
AU  - Doi M
AD  - Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical 
      Factory, Inc. Muya-cho, 772-8601, Naruto, Tokushima, Japan. doims@otsukakj.co.jp
FAU - Yamaoka, Ippei
AU  - Yamaoka I
FAU - Fukunaga, Tetsuya
AU  - Fukunaga T
FAU - Nakayama, Mitsuo
AU  - Nakayama M
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Amino Acids)
RN  - 0 (Blood Glucose)
RN  - 04Y7590D77 (Isoleucine)
RN  - GMW67QNF9C (Leucine)
RN  - HG18B9YRS7 (Valine)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Administration, Oral
MH  - Amino Acids/administration & dosage/pharmacology
MH  - Animals
MH  - Blood Glucose/*analysis/*drug effects
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Glucose/*metabolism
MH  - Glucose Tolerance Test
MH  - Isoleucine/*administration & dosage/pharmacology
MH  - Leucine/*administration & dosage/pharmacology
MH  - Male
MH  - Muscle Fibers, Skeletal/drug effects/*metabolism
MH  - Myoblasts/drug effects/*metabolism
MH  - Plasma/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Valine/*administration & dosage/pharmacology
EDAT- 2003/12/04 05:00
MHDA- 2004/03/19 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/03/19 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - S0006291X03024045 [pii]
AID - 10.1016/j.bbrc.2003.11.039 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2003 Dec 26;312(4):1111-7. doi: 
      10.1016/j.bbrc.2003.11.039.