Leucine promotes glucose uptake in skeletal muscles of rats.
Soleus muscles isolated from normal rats were incubated to evaluate whether or not leucine promotes glucose uptake under insulin-free conditions, using a labeled 2-deoxyglucose uptake assay. Glucose uptake was promoted by 2mM leucine. A metabolite of leucine, alpha-ketoisocaproic acid (alpha-KIC), also exhibited a similar stimulatory effect, although this was not as potent as leucine. Stimulation of glucose uptake by leucine was completely canceled by pre-treatment with either 10 microM LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), or 6 microM GF109203X, a specific inhibitor of protein kinase C (PKC). No significant change was observed by pre-treatment with 1 microM rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR). These results suggest that leucine stimulates glucose transport in skeletal muscle via PI3-kinase and PKC pathways independently of the mammalian target of mTOR. They also suggest that leucine stimulates glucose transport by an insulin-independent mechanism.
Nishitani
Shinobu
S
Pharmaceutical Research Laboratories, Ajinomoto Co., Inc., 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki-shi, Kanagawa 210-8681, Japan. shinobu_nishitani@ajinomoto.com
Matsumura
Tsuyoshi
T
Fujitani
Shoji
S
Sonaka
Ichiro
I
Miura
Yutaka
Y
Yagasaki
Kazumi
K
D000818:Animals; D001692:Biological Transport; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007651:Keto Acids / Q000494:pharmacology; D007930:Leucine / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007328:Insulin; D007651:Keto Acids; C013082:alpha-ketoisocaproic acid; D007930:Leucine; D005947:Glucose