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( van Loon, Saris, Verhagen, & Wagenmakers, 2000 ) suggesting a central
role for glutamine in amino acid-mediated insulin secretion.
Amino acid combinations also appear to increase insulin response in the
presence of glucose. van Loon et al. (2000) fed eight healthy males mixtures
of free amino acids (arginine, glutamine, leucine, phenylalanine) and protein
hydrolysates (whey, pea, wheat, casein) along with a standard amount of glu-
cose (114.2 g/L) and measured insulin. The study showed that the ingestion
of protein with carbohydrate increased insulin expression by nearly 100%
compared to carbohydrate alone. Leucine, phenylalanine, and arginine were
particularly insulinogenic when consumed with carbohydrates. The study
also showed that the insulin response was significantly positively correlated
with plasma leucine, phenylalanine, and tyrosine concentrations. In an
in vitro study, insulin secretion was augmented when a perfused rat pancreas
was exposed to 2, 5 and 10 mM of leucine and isoleucine in the presence
5.6 mM of glucose ( Pek, Santiago, & Tai, 1978 ) .
The greater insulinotropicity of certain food proteins may also be due to
synergistic associations between amino acids comprised in each. Gannon
et al. (1988) observed that gelatin induced a insulin release that was approx-
imately 270%more than that seen for glucose. Approximately 55-65% of the
amino acids in gelatin are made up of glycine, proline, and hydroxyproline
and it is therefore reasonable to postulate that the insulinotropicity of gelatin
is largely due to these amino acids. However, individual administration of
these amino acids (with or without glucose) had little effect on insulin secre-
tion ( Gannon et al., 2002a; Nuttall et al., 2004 ). This suggests that the
enhanced insulinotropicity of gelatin may be due to synergistic effects
between these amino acids. Gannon et al. (1988) also showed that cottage
cheese potentiated an insulin response that was 360% greater than that of
glucose. The predominant protein in cottage cheese is casein and this is
relatively rich in proline and phenylalanine compared to other proteins
( Lavigne, Marette, & Jacques, 2000 ) . Phenylalanine and proline alone or
in combination with glucose had relatively smaller effects on insulin secre-
tion. Therefore, the greater effects seen with casein may be again due to
synergism. Milk proteins have been shown to be more insulinogenic
( Elmstahl & Bjorck, 2001 ) , particularly the whey fraction ( Nilsson,
Stenberg, Frid, Holst, & Bjorck, 2004 ). While this may be due to synergistic
associations between the amino acids in dairy proteins, whey protein, in par-
ticular, has shown to also induce a greater incretin response ( Nilsson et al.,
2004 ). Whey proteins independently stimulate GLP-1 and gastric inhibitory
peptide (GIP) secretion which can, in turn, influence insulin expression
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