Role of Proteins in Insulin Secretion and Glycemic Control - Advances in Food and Nutrition Research - page 18

to 10 mM of valine, leucine, or isoleucine. Studies using rodent-derived
BRIN-BD11 cells showed that 1 and 10 mM of alanine, arginine, gluta-
mine, glycine, leucine, lysine, proline, and serine all increased insulin
expression by up to fivefold in the presence of nonstimulatory glucose levels.
Glutamine was also shown to be insulinogenic by Li et al. (2004) using
mouse islet cells. The authors suggest that glutamine may be playing a central
role (as a signaling molecule) in amino acid- and glucose-stimulated insulin
secretion. Glutamic acid is one of few amino acids present in relatively
higher amounts in the plasma irrespective of time of day and meal compo-
sition, and is omnipresent in considerable amounts in food proteins
( Wurtman, Rose, Chou, & Larin, 1968 ) . Therefore, it is possible that glu-
tamine plays a central role in amino acid-mediated insulin secretion. There
appear to be no human studies evaluating the effect of glutamate on insulin
secretion possibly due to gastrointestinal distress caused by it at physiological
doses ( Gannon & Nuttall, 2010 ). Interestingly, cysteine has been shown to
inhibit insulin expression. Kaneko, Kimura, Kimura, and Niki (2006)
exposed mouse islet cells to L -cysteine and found that it reduced insulin
expression presumably due to the production of H 2 S by the amino acid.
However, these findings remain to be confirmed in human trials.
Human studies investigating amino acid effects on insulinemia provide
the most reliable data however, and these show different results to rodent
studies. A review by Gannon and Nuttall (2010) included a hierarchical list
of insulinogenic amino acids They reported that the most insulinogenic
amino acids are phenylalanine and glycine and the least insulinogenic, argi-
nine, tyrosine, and histidine. There is limited information from human stud-
ies on aspartic acid, asparagine, tryptophan, ornithine, threonine, serine,
tyrosine, and histidine on human insulin secretion, and no data on the
impact of cysteine and selenocysteine. Cysteine analogues have been shown
to stimulate insulin from rat pancreatic islets ( Ammon, Hehl, Enz, Setiadi-
Ranti, & Verspohl, 1986 ) and this requires confirmation in human studies.
Interestingly, these findings are opposite to those reported by Kaneko et al.
(2006) . Although cysteine is found in very small quantities in food proteins
investigating higher than physiological doses on insulin, secretion may pro-
duce therapeutically useful data. It may also be interesting to investigate
selenocysteine's effects on insulin secretion as Selenium has been shown
to stimulate insulin ( Iizuka, Sakurai, & Hikichi, 1992 ) and hold insulin
mimetic properties ( Stapleton, 2000 ) .
A considerable number of studies have shown that two or more amino
acids increase insulin secretion through synergy. Early work carried out by