No 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.

The majority of individual amino acids increase insulin and attenuate the plasma glucose response when ingested with glucose. Objective. To determine whether ingestion of two amino acids simultaneously, with glucose, would result in an additive effect. Leucine (Leu) and glycine (Gly) were chosen because they were two of the most potent glucose-lowering amino acids when given individually. Materials and Methods. Nine subjects received test items on four separate days. The first was a water control, then 25 g glucose, or Leu + Gly (1 mmol/kg fat-free mass each) ±25 g glucose, in random order. Glucose, insulin, and glucagon were measured frequently for 2.5 hours. Net areas were calculated. Results. The glucose area response decreased by 66%. The insulin area response increased by 24% after ingestion of Leu + Gly + glucose compared to ingestion of glucose alone. The decrease in glucose response was not additive; the increase in insulin response was far less than additive when compared to previously published individual amino acid results. The glucagon concentration remained unchanged. Conclusion. There is an interaction between Leu and Gly that results in a markedly attenuated glucose response. This occurred with a very modest increase in insulin response. Changes in glucagon response could not explain the results. The mechanism is unknown.

Leucine (Leu) is well recognized to stimulate insulin secretion and to reduce the glucose rise when ingested with glucose. Glycine (Gly) reduces the glucose rise, but only weakly stimulates insulin secretion. We have shown that both were particularly potent in their ability to attenuate the glucose response to 25 g glucose. The current study was designed to determine whether the glucose‐attenuating effects would be even greater if Gly and Leu were ingested together with glucose. On 4 separate days, 9 healthy subjects were studied. Test meals were given at 0800 hr. Subjects received water only on day 1, followed by 25 g glucose only, Leu + Gly (1 mmol/kg fat free body mass each), or Leu + Gly with 25 g glucose, on subsequent days in random order. Serum/plasma glucose, insulin and glucagon were measured frequently thereafter for 2.5 hrs. Net areas under the curve were calculated. The glucose area response decreased by 77% (p<0.02) after ingestion of Leu + Gly + glucose compared to ingestion of glucose alone. The insulin area response increased by only 24% (p<0.05). When compared to our previously published data on the individual amino acids, the decrease in glucose response with Leu + Gly + glucose was partially additive. The increase in insulin response was less than additive. The glucagon response was considerably less than additive. Thus, there is a mechanistic interaction between Leu and Gly when ingested with glucose that results in a markedly attenuated glucose response. This occurred in the presence of an attenuated insulin response. Changes in glucagon response could not explain the results. Overall, the way in which ingested amino acids interact with each other and affect glucose metabolism is complex and not well understood. Grant Funding Source: Supported in part by Funds from the Department of Veterans Affairs