Ingestion of Leucine + Phenylalanine with Glucose Produces an Additive Effect on Serum Insulin but Less than Additive Effect on Plasma Glucose

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. 1. Introduction In a series of studies, our laboratory has quantified the ability of single amino acids, when ingested at 1.0？mmol/kg fat-free body mass with or without 25？g of glucose, to stimulate a rise in insulin and/or glucagon. Also, when ingested with glucose, their potential to attenuate the glucose area response integrated over a 2.5-hour period of time was determined. Sixteen amino acids were studied. The potency of the individual amino acids in regard to their effect on the insulin, glucagon, and glucose concentrations varied greatly between amino acids, and the specific responses could not be predicted based on the structure of the amino acids [1]. Leucine and phenylalanine were particularly potent in their ability to attenuate the glucose response to 25？g of glucose. Therefore, we were interested in determining if the glucose-attenuating effect would be greater if these two amino acids were ingested together with glucose. We were particularly interested in whether the effects would be additive. The effects of these amino acids on the insulin and glucagon responses also were monitored. 2. Methods Eight healthy subjects