Role of Proteins in Insulin Secretion and Glycemic Control - Advances in Food and Nutrition Research - page 19

Floyd et al. (1966b) showed that amino acid combinations induced greater
insulin secretion than single amino acids. A combination of 10 essential
amino acids produced a maximal insulin increase of 120 m U/ml compared
to when the same amino acids were given separately (which produced a
maximal ranging between 3 and 80 m U/ml). Similarly, 30 g portions of
six to eight amino acid containing mixes produced significantly greater
plasma insulin responses compared to when given alone. To test the syner-
gistic effects of amino acids, Floyd et al. (1970) conducted an experiment
using 11 healthy young males. The subjects were given 15 g intravenous
infusions of one or two amino acids and insulin was measured. Infusing
two amino acids produced a greater insulin response than the sum of the
separate effects. Arginine and leucine, and arginine and phenylalanine were
particularly good synergistic combinations. Arginine given with casein
increased the total insulin response in rats in another study ( Sugano,
Ishiwaki, Nagata, & Imaizumi, 1982 ) . Arginine combined with lysine or his-
tidine, and leucine and histidine did not produce synergistic effects. However,
Isidori et al. (1981) measured the insulin response in 15 healthy males follow-
ing an oral dose of lysine and arginine (1200 mg of each) and found that their
combination resulted in a greater insulin response than when each was given
separately. Sugano et al. (1982) showed that soya bean protein given in com-
bination with lysine increased total insulin secretions. Floyd, Fajans, Conn,
Knopf, and Rull (1966a) fed healthy participants 500 g of either beef or
chicken liver and found that plasma insulin and leucine increased markedly.
The magnitude of the insulin rise was far greater than that seen with leucine
alone in previous studies suggesting a possible synergistic effect between
amino acids found in the proteins. For example, these proteins are also good
sources of arginine, lysine, and glutamine. Other studies have shown that
glutamine in combination with leucine significantly augments insulin secre-
tion ( Sener, Somers, Devis, & Malaisse, 1981 ) . Although glutamine has been
shown to be poorly insulinogenic in some work ( Gannon & Nuttall, 2010 ),
others show that it can induce insulin in the presence of allosteric GDH
activators ( Newsholme et al., 2005 ) . It is possible therefore that leucine and
glutamine synergistically increase insulin secretion by increasing catabolic
fluxes and the former acting as an allosteric activator of GDH ( Malaisse
et al., 1982 ) . In vitro work using mouse islet cells showed that a leucine ramp
(0-25 mM) in the presence of 2-mM glutamine increased insulin secretion by
10-fold although a glutamine ramp (0-25 mM) alone had no effect on insulin
( Li et al., 2004 ). Other in vitro cell studies showed that both arginine
and phenylalanine strongly stimulate insulin in the presence of glutamine