Abstract
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.
Materials and 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 (Ser473), total and plasma membrane GLUT4 content, total and p-AMPK-α and p-ACC (Ser79), p-GSK-3α/β (Ser21/9) 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 (Ser473), total and p-AMPK-α and ACC, and nNOS expression.
Conclusion
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.
Abbreviations:
ACC (Acetyl-CoA Carboxylase), Akt (Protein Kinase B), AMPK (AMP-activated Protein Kinase), Arg (L-Arginine), c-GMP (Cyclic-Guanylil Monophosphate), D-Man (D-Mannitol), EDL (Extensor Digitorum Longus Muscle), eNOS (Endothelial Nitric Oxide Synthase), FBS (Fetal Bovine Serum), GAPDH (Glyceraldehydes 3-Phosphate Dehydrogenase), GH (Growth Hormone), GLUT4 (Glucose Transporter Type 4), GSK-3α/β (Glycogen Synthase Kinase alpha and beta), iNOS (Inducible Nitric Oxide Synthase), IRS (Insulin Receptor Substrate), L-NAME (NG-Nitro-L-arginine methyl ester), Lys (L-Lysine), nNOS (Neuronal Nitric Oxide Synthase), NO (Nitric Oxide), NOS (Nitric Oxide Synthase), PI3-K (Phosphatidylinositol 3-Kinase), SNP (Sodium Nitroprusside), SP (Spermine NONOate), α-MEM (Modified Eagle Medium)Keywords
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Article info
Publication history
Published online: August 13, 2012
Accepted:
June 27,
2012
Received:
February 27,
2012
Identification
Copyright
© 2013 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
