Amino acids and insulin are both required to regulate assembly of the eIF4E. eIF4G complex in rat skeletal muscle.
The respective roles of insulin and amino acids in regulation of skeletal muscle protein synthesis and degradation after feeding were examined in rats fasted for 17 h and refed over 1 h with either a 25 or a 0% amino acid/protein meal. In each nutritional condition, postprandial insulin secretion was either maintained (control groups: C(25) and C(0)) or blocked with diazoxide injections (diazoxide groups: DZ(25) and DZ(0)). Muscle protein metabolism was examined in vitro in epitrochlearis muscles. Only feeding the 25% amino acid/protein meal in the presence of increased plasma insulin concentration (C(25) group) stimulated protein synthesis and inhibited proteolysis in skeletal muscle compared with the postabsorptive state. The stimulation of protein synthesis was associated with increased phosphorylation of eukaryotic initiation factor (eIF)4E binding protein-1 (4E-BP1), reduced binding of eIF4E to 4E-BP1, and increased assembly of the active eIF4E. eIF4G complex. The p70 S6 kinase (p70(S6k)) was also hyperphosphorylated in response to the 25% amino acid/protein meal. Acute postprandial insulin deficiency induced by diazoxide injections totally abolished these effects. Feeding the 0% amino acid/protein meal with or without postprandial insulin deficiency did not stimulate muscle protein synthesis, reduce proteolysis, or regulate initiation factors and p70(S6k) compared with fasted rats. Taken together, our results suggest that both insulin and amino acids are required to stimulate protein synthesis, inhibit protein degradation, and regulate the interactions between eIF4E and 4E-BP1 or eIF4G in response to feeding.
Balage
M
M
Institut National de la Recherche Agronomique, Unité de Nutrition et Métabolisme Protéique, 63122 Saint Genes Champanelle, France. balage@clermont.inra.fr
Sinaud
S
S
Prod'homme
M
M
Dardevet
D
D
Vary
T C
TC
Kimball
S R
SR
Jefferson
L S
LS
Grizard
J
J
D000596:Amino Acids / Q000008:administration & dosage / Q000097:blood / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology; D004044:Dietary Proteins / Q000008:administration & dosage; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D005215:Fasting; D005502:Food; D007328:Insulin / Q000097:blood / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000378:metabolism*; D010750:Phosphoproteins; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism
D000596:Amino Acids; D001786:Blood Glucose; D002352:Carrier Proteins; D004044:Dietary Proteins; C499526:Eif4ebp1 protein, rat; D039561:Eukaryotic Initiation Factor-4E; D039603:Eukaryotic Initiation Factor-4G; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D010448:Peptide Initiation Factors; D010750:Phosphoproteins; D019893:Ribosomal Protein S6 Kinases; D003981:Diazoxide