L-Arginine enhances glucose and lipid metabolism in rat L6 myotubes via the NO/ c-GMP pathway

Autor(es)

Barbosa, Thais de Castro ^{[1, 2, 3]} ; Jiang, Lake Q. ^{[2, 3]} ; Zierath, Juleen R. ^{[2, 3]} ; Nunes, Maria Tereza ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Physiol & Biophys, BR-05508 Sao Paulo - Brazil

^[2] Karolinska Inst, Dept Mol Med & Surg, Sect Integrat Physiol, S-17177 Stockholm - Sweden

^[3] Karolinska Inst, Dept Mol Med & Surg, Sect Integrat Physiol, Stockholm - Sweden

• Tipo de documento: Artigo Científico
• Fonte: METABOLISM-CLINICAL AND EXPERIMENTAL; v. 62, n. 1, p. 79-89, JAN 2013.
• Citações Web of Science: 15

Resumo

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 Argon 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 mu mol/L) and L-NAME (100 mu mol/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-alpha and p-ACC (Ser(79)), p-GSK-3 alpha/beta (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-alpha and ACC, and nNOS expression. Conclusion. We provide evidence that Mg improves glucose and lipid metabolism in skeletal muscle, in parallel with increased phosphorylation of Akt and AMPK-alpha. 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. (C) 2013 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 07/53458-3 - Avaliação das bases moleculares envolvidas nos efeitos da administração oral crônica do aminoácido arginina sobre a sensibilidade insulínica: repercussões sobre os tecidos muscular esquelético, cardíaco, adiposo, hepático e sobre a secreção de insulina
• Beneficiário: Thais de Castro Barbosa
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto