898
Koopman et al.
2.2 Protein and Amino Acids
Amino acids have more metabolic roles than to
merely serve as building blocks for de novo protein
synthesis. Amino acids stimulate the secretion of
insulin, glucagon, growth hormone and IGF-1.
[47]
The intravenous administrations of amino acids
in vivo in humans was shown to result in a signifi-
cant increase in plasma insulin levels.
[48-51]
More
recently, reports from our laboratory show that co-
ingestion of a protein hydrolysate with or without
additional leucine and phenylalanine with carbohy-
drate effectively increases the plasma insulin secre-
tion in patients diagnosed with long-term type 2
diabetes mellitus,
[52]
healthy sedentary controls
[53]
and endurance-trained athletes.
[34,35]
Amino acids
and leucine in particular, can act as potent stimuli
for the secretion of insulin from the pancreatic
cell. The various mechanisms by which amino acids
promote and/or enhance insulin secretion are di-
verse and have not yet been fully elucidated.
[54]
Similar to glucose-mediated insulin secretion,
[55]
in-
tracellular catabolism of the metabolisable amino
acids will increase substrate availability for the tri-
carboxylic acid (TCA) cycle. Increased TCA cycle
PI3-K
Akt
mTOR
Insulin/IGF-1
eIF4E·4E-BP1
S6K1
S6
Translation initiation
Protein synthesis
eIF2·GTP
eIF2
·
GDP
eIF2B
GSK-3
Exercise
AMPK
Amino acids
Leucine
mGCN2
Nutrition
eIF4F
Fig. 2. The integration of signals from exercise and nutritional fac-
tors. The solid lines represent a direct effect and the dashed lines
represent an indirect effect (reproduced from Koopman,
[64]
with per-
mission). 4E-BP1 = eIF4E binding protein 1; Akt = protein kinase B;
AMPK = adenosine monophosphate-activated kinase; eIF2B =
eukaryotic initiation factor 2B; eIF2
·
GDP = inactive eukaryotic initi-
ation factor 2; eIF2
·
GTP = activated eukaryotic initiation factor 2;
eIF4E = eukaryotic initiation factor 4E; eIF4F = eukaryotic initiation
factor 4F; GSK-3 = glycogen synthase kinase-3; IGF-1 = insulin-like
growth factor-1; mGCN2 = mammalian ortholog of the yeast gener-
al control non-depressing kinase 2; mTOR = mammalian target of
rapamycin; PI3-K = phosphatidylinositol-3 kinase; S6 = ribosomal
protein S6; S6K1 = p70/p85 ribosomal protein S6 protein kinase.
activity and oxidative phosphorylation will result in
an increased adenosine triphosphate (ATP)/adeno-
ure 2). Biolo et al.
[59]
demonstrated that hyperami-
sine diphosphate ratio, which will lead to the closing
noacidaemia, resulting from intravenous infusion of
of ATP-sensitive K
+
channels. The latter will lead to
amino acids, increases post-exercise muscle protein
the depolarisation of the plasma membrane, thereby
synthesis rates and prevents the exercise-induced
opening up voltage-activated Ca
2+
channels, result-
increase in protein degradation. Moreover, amino
ing in Ca
2+
-activated insulin exocytosis. Leucine-
acid infusion in the fasted state, in the absence of
induced insulin secretion is mediated by its oxida-
prior (resistance) exercise, rapidly increases muscle
tive decarboxylation as well as by its ability to allos-
protein synthesis rates.
[9]
Since intravenous amino
terically activate glutamate dehydrogenase.
[54,56,57]
acid infusion does not represent a practical method
Both the generation of acetyl-coenzyme A and
-
for amino acid delivery, oral administration of pro-
ketoglutarate are needed for leucine to fully stimu-
tein and/or amino acid mixtures has since been
late mitochondrial activity in the pancreatic
-cell.
studied intensively. The ingestion of a large amount
The metabolically linked secondary signals that sub-
(3040g) of amino acids after exercise effectively
sequently lead to insulin exocytosis remain to be
stimulates muscle protein synthesis.
[60]
Moreover,
established, and seem also responsible for the leu-
ingestion of smaller amounts of essential amino
cine-induced activation of the mammalian target of
acids (EAAs) with and without carbohydrate has
rapamycin (mTOR) signalling pathway.
[57,58]
also been shown to augment post-exercise protein
There is a substantial amount of evidence that
synthesis and improve net protein balance.
[61-63]
supplementation with protein/amino acids can effec-
Thus, post-exercise amino acid ingestion represents
tively stimulate muscle protein synthesis rates (fig-
an effective method to maximise the anabolic re-
©
2007 Adis Data Information BV. All rights reserved.
Sports Med 2007; 37 (10)
Study 