Role of Proteins in Insulin Secretion and Glycemic Control - Advances in Food and Nutrition Research - page 16

found that leucine hypersecreted insulin in obese hyperinsulinaemic
children compared to normal children. Similar findings were reported
by Kelly et al. (2001) and the authors attributed this to impaired physiology
of glutamate dehydrogenase (GDH), an enzyme linked with leucine-
induced insulin secretion. Indeed, Li et al. (2003) demonstrated that b -cell
sensitivity to leucine depends upon GDH activation. The method of insu-
lin secretion by leucine has been suggested to be different to that of other
amino acids ( Fajans,Floyd,Knopf,Guntsche,etal.,1967 ). Leucine has
been shown to stimulate b -cells by increasing mitochondrial metabolism
through GDH activation which increases ATP through transamination
of leucine into a -ketoisocaproate ( Newsholme et al., 2005 ). Leucine
metabolism has also been suggested to activate the mTOR signaling path-
way in b -cells and stimulate insulin.
In summary, the literature suggests that leucine stimulates insulin secre-
tion by b -cells even in the absence of glucose. There appears to be a dose-
response relationship between plasma leucine and insulin secretion in
normal subjects. However, this may be impaired in those with physiological
disorders. Leucine at levels usually found in food appears to have only a
modest effect on insulin secretion.
Phenylalanine is a nonpolar essential amino acid found in most animal
and plant proteins. Early work carried out by Floyd et al. (1966b) showed
that a 30 g intravenous infusion of phenylalanine modestly increased insulin
secretion (maximal increase 28 m U/ml). G ¨ ttler, K ¨ hl, Pedersen, and P˚by
(1978) demonstrated that similar effects can be observed also by far smaller
phenylalanine doses. The authors gave six healthy adult males oral doses of
0.6 mM/kg body weight of phenylalanine. Insulin and glucagon levels
began rising within 10 min of amino acid ingestion and peaked at twice
the baseline level at 30 min. The study also observed a concomitant increase
in serum tyrosine which maximized at 2 h. Nuttall, Schweim, and Gannon
(2006) gave six healthy subjects 1 mM/kg body weight of phenylalanine and
measured insulin and glucagon for the following 2.5 h. The authors
observed a significant increment in insulin secretion following phenylala-
nine compared to the water control. However, the temporal insulin
response pattern differed from that seen by G ¨ ttler et al. in that phenylala-
nine induced a 10-min initial lag followed by a high and sustained response
during the remaining period. Phenylalanine also stimulated a significant rise
in glucagon (approximately 2000 pg/min/ml) compared to the control.
In vitro studies show less conclusive effects. In one study, 5-80 mM of phe-
nylalanine did not stimulate a significant insulin secretion from perfused