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show conflicting results. Bolea, Pertusa, Mart ´ n, Sanchez-Andr ´ s, and Soria
(1997) found that isoleucine stimulated insulin secretion in fresh mouse islet
cells as did one and 10 mM/L concentrations in BRIN-BD-11 cells
( McClenaghan, Barnett, O'Harte, & Flatt, 1996 ). However, Milner (1970)
found no significant effects when rabbit pancreas was incubated in medium
containing 5 mM of isoleucine. These studies predominantly suggest that
isoleucine alone has little effect on human insulin secretion. However, this
conclusion is based on a small number of studies.
Leucine is one of the most extensively studied BCAAs. It has been shown
to play a notable role in insulin-induced mRNA translation and skeletal
muscle synthesis ( Kimball, Farrell, & Jefferson, 2002 ) . Studies have also con-
clusively shown that leucine in combination with glucose significantly
upregulates insulin secretion. However, a fewer number of studies have
looked at the effects of leucine alone on insulin. Milner (1970) reported that
leucine was the only essential amino acid that stimulated insulin in the
absence of glucose. A study published by Fajans, Knopf, Floyd, Power,
and Conn (1963) studied the effect of 0.2 g/kg of body weight of leucine
on insulin secretion in healthy subjects. They found that both intravenous
and oral doses were insulinogenic. These results were confirmed in another
study by the same group using 30-g intravenous boluses on 10 healthy
humans ( Floyd et al., 1966b ). Kalogeropoulou, Lafave, Schweim,
Gannon, and Nuttall (2008) gave 13 healthy subjects 1 mM/kg lean body
mass leucine and measured insulin for the subsequent 2.5 h. The study
reported a small but significant increase (approximately 200 m U/min/ml)
in insulin compared to a water control. It also resulted in a significant
increment in glucagon. McArthur, Kirtley, and Waife (1963) gave two
healthy males oral doses of leucine at various levels and found that higher
levels (750 mg/kg body weight) induced hypoglycemia while lower levels
(150 mg/kg body weight) did not. While the results suggest that high levels
of leucine may be insulinogenic, this cannot be confirmed as the study did not
measure insulin. Interestingly, Cochrane, Payne, Simpkiss, and Woolf (1956)
showed that those with idiopathic hypoglycemia were more sensitive to
leucine and showed marked reductions in blood glucose when given
150 mg/g body weight of leucine, compared to normal subjects. Since leu-
cine's influence on blood sugar has been indicated to be through its effects
on insulin ( Fajans et al., 1963 ) this suggests that those with idiopathic hypo-
glycemia may be producing more insulin in response to leucine. Indeed, other
studies have shown that leucine upregulates insulin secretion in those
with disordered metabolism. Loridan, Sadeghi-Nejad, and Senior (1971)
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