L-Arginine enhances glucose and lipid metabolism in rat L6 myotubes via the NO/ c-GMP pathway.
OBJECTIVE
The amino acid Arginine (Arg) is the main biological precursor of nitric oxide (NO) and has been described to improve insulin sensitivity in diabetes and obesity. We investigated the molecular mechanisms involved in the long-term effects of Arg on glucose and lipid metabolism.


METHODS
L6 myotubes were treated with Arg (7 mmol/L) for 6 days. D-Mannitol (7 mmol/L) was used as control; spermine NONOate (10 μmol/L) and L-NAME (100 μmol/L) were used to evaluate the NO/c-GMP pathway role. Basal and insulin-induced (120 nmol/L) glycogen synthesis, glucose uptake and lipid oxidation, c-GMP and nitrite levels, and the intracellular signaling pathways were evaluated.


RESULTS
Arg-treatment increased: 1) basal and insulin-stimulated glycogen synthesis; 2) glucose uptake; 3) palmitate oxidation; 4) p-Akt (Ser(473)), total and plasma membrane GLUT4 content, total and p-AMPK-α and p-ACC (Ser(79)), p-GSK-3α/β (Ser(21/9)) and 5) nitrite and c-GMP levels. L-NAME treatment suppressed Arg effects on: 1) nitrite and c-GMP content; 2) glycogen synthesis and glucose uptake; 3) basal and insulin-stimulated p-Akt (Ser(473)), total and p-AMPK-α and ACC, and nNOS expression.


CONCLUSIONS
We provide evidence that Arg improves glucose and lipid metabolism in skeletal muscle, in parallel with increased phosphorylation of Akt and AMPK-α. These effects were mediated by the NO/c-GMP pathway. Thus, arginine treatment enhances signal transduction and has a beneficial effect of metabolism in skeletal muscle through direct activation of Akt and AMPK pathways.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Thais
T
de Castro Barbosa
Lake Q
LQ
Jiang
Juleen R
JR
Zierath
Maria Tereza
MT
Nunes
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013096:Spermine / Q000031:analogs & derivatives* / Q000494:pharmacology
D051275:Glucose Transporter Type 4; C495694:Slc2a4 protein, rat; C091861:spermine nitric oxide complex; D013096:Spermine; D001120:Arginine; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D055372:AMP-Activated Protein Kinases; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester