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Received May 25, 2004
Revised June 18, 2004
Accepted after revision October 27, 2004
1 Institut National de la Recherche Agronomique
2 Laboratoire de Biochimie, Biologie Mol&eculaire et Nutrition, Facult& de Pharmacie, Clermont-Ferrand
3 Department of cellular and molecular physiology, Pennsylvania State University College of Medicine,
* To whom correspondence should be addressed. E-mail: balage{at}clermont.inra.fr.
The potential respective role of insulin and dietary amino acids in the regulation of skeletal muscle protein synthesis was examined in adult and old rats. Animals were fed over 1-h with either a 25% or a 0% amino acid/protein meal. In each nutritional condition, postprandial insulin secretion was either maintained or blocked with diazoxide injections. Protein synthesis in gastrocnemius and soleus muscles was assessed in vivo using the flooding dose method. Insulin suppression decreased protein synthesis in both muscles irrespective of the nutritional condition and the age of the rats. Moreover, reduced insulinemia was associated with 4E-BP1 dephosphorylation, enhanced assembly of the 4E-BP1.elF4E inactive complex and hypophosphorylation of elF4E, p70S6k and PKB. Old rats did not differ from adult rats. The lack of amino acids in the meal of insulin-suppressed rats did not result in any additional decrease in protein synthesis. In the presence of insulin secretion, dietary amino acid suppression decreased significantly gastrocnemius protein synthesis in adult but not in old rats. Amino acid suppression was associated with reduced phosphorylation of 4E-BP1 and p70S6k in adults. Along with protein synthesis, only the inhibition of p70S6k phosphorylation was abolished in old rats. We concluded that insulin is required for the regulation of muscle protein synthesis irrespective of age and that the effect of dietary amino acids is blunted in old rats.
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