Ingestion of leucine + phenylalanine with glucose produces an additive effect on serum insulin but less than additive effect on plasma glucose

Abstract

Most individual amino acids stimulate insulin secretion and attenuate the plasma glucose response when ingested with glucose. We determined whether ingestion of two amino acids simultaneously with glucose would result in an additive effect on the glucose area response compared with ingestion of amino acids individually. Leucine and phenylalanine were chosen because they were two of the most potent glucose-lowering amino acids when given individually. Eight healthy subjects were studied on four separate days. Test meals were given at 0800. The first meal was a water control. Subjects then received 25 g glucose or leucine + phenylalanine (1 mmol/kg fat free body mass each) ±25 g glucose in random order. Glucose, insulin and glucagon were measured frequently for 2.5 hours thereafter. Net areas under the curves were calculated using the mean fasting value as baseline. The insulin response to leucine + phenylalanine was additive. In contrast, the decrease in glucose response to leucine + phenylalanine + glucose was less than additive compared to the individual amino acids ingested with glucose. Interestingly, the insulin response to the combination was largely due to the leucine component, whereas the glucose response was largely due to the phenylalanine component. Glucose was unchanged when leucine or phenylalanine, alone or in combination, was ingested without glucose. This trial is registered with ClinicalTrials.gov NCT01471509.

Figures

Figure 1

(a) Mean (±SEM) plasma glucose concentration in 8 healthy subjects after ingestion of water only (open circles), 25 g glucose (closed circles), leucine + phenylalanine at 1 mmol/kg fat-free mass each (open triangles), or 25 g glucose with leucine + phenylalanine at 1 mmol/kg fat-free mass each (closed triangles). Insert left—previous data with leucine alone [2]. Insert right—previous data with phenylalanine alone [3]. (b) Net-integrated AUC using the fasting values as baseline. Bars with different letters indicate that values are significantly different (P < 0.05).

Figure 2

(a) Mean (±SEM) serum insulin concentration in 8 healthy subjects after ingestion of water only (open circles), 25 g glucose (closed circles), leucine + phenylalanine at 1 mmol/kg fat-free mass each (open triangles), or 25 g glucose with leucine + phenylalanine at 1 mmol/kg fat-free mass each (closed triangles). Insert left—previous data with leucine alone [2]. Insert right—previous data with phenylalanine alone [3]. (b) Net-integrated AUC using the fasting values as baseline. Bars with different letters indicate that values are significantly different (P < 0.05).

Figure 3

(a) Mean (±SEM) plasma glucagon concentration in 6 healthy subjects after ingestion of water only (open circles), 25 g glucose (closed circles), leucine + phenylalanine at 1 mmol/kg fat-free mass each (open triangles), or 25 g glucose with leucine + phenylalanine at 1 mmol/kg fat-free mass each (closed triangles). (b) Net-integrated AUC using the fasting values as baseline. Bars with different letters indicate that values are significantly different (P < 0.05).