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in insulin concentration that corresponded with a rise in glucose con-
centration). This suggests that glycine alone cannot be credited for the
insulinotropic effect of gelatin.
Intravenous studies showed that out of a mix of amino acids, arginine was
the most potent in increasing circulating insulin concentrations and decreas-
ing blood glucose in healthy subjects ( Floyd et al., 1966a ) . Arginine admin-
istered with glucose attenuated blood glucose concentrations. In another
study, Floyd et al. (1970) showed that arginine brought about the greatest
insulin release in healthy subjects compared to histidine and leucine
(all given as 30 g doses). Arginine given as an intraduodenal infusion to
healthy volunteers resulted in an increase in serum insulin while blood
glucose concentrations did not change ( Dupre et al., 1968 ) . The effect of
L -arginine administered orally on blood glucose concentrations in healthy
subjects was investigated in another study ( Gannon et al., 2002b ) . L -arginine
was given with and without glucose on two separate occasions. When
L -arginine was ingested with glucose, it attenuated and prolonged the blood
glucose rise. The study showed that arginine did not stimulate an increase in
insulin when ingested alone and neither did it synergize when ingested with
glucose to stimulate insulin secretion. Arginine was shown to induce large
increases in plasma citrulline along with reduced glucose production
( Apostol & Tayek, 2003 ). The production of citrulline and nitric oxide from
arginine seemed to play important roles in blood glucose regulation.
An in vitro study with isolated rat islets in 1980 showed that in the presence
of glucose, arginine potentiated the effect of glucose which increased with
increasing amino acid concentrations ( Khalid & Rahman, 1980 ) . Other
in vitro studies showed that the stimulation of insulin by arginine was depen-
dent on the ambient glucose concentration ( Blachier et al., 1989; Levin,
Grodsky, Hagura, Smith, & Forsham, 1972 ). However, human studies
showed that arginine ingested with glucose did not stimulate insulin secre-
tion and attenuated the blood glucose rise ( Gannon et al., 2002a,2002b ).
This attenuation was not caused by delayed gastric emptying and the mech-
anism remains to be determined. Arginine also stimulated a modest increase
in glucagon concentration when ingested alone, and a decrease when
ingested with glucose ( Gannon et al., 2002b ) . Arginine's effects on insulin
secretion remains equivocal. However, it appears to play a notable role in
blood glucose control through its effects on metabolic pathways.
Leucine has been long known as a potent insulin secretagogue ( Fajans
et al., 1963; Floyd et al., 1966a; McArthur et al., 1963 ) . Intravenous
administration of 30 g leucine with 30 g glucose was
reported to
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