Intragastric lysine lowers the circulating glucose and insulin responses to a mixed-nutrient drink without slowing gastric emptying in healthy adults

Abstract

Background: Lysine is reported to lower the glycemic response to oral glucose in humans and, albeit at high loads, to slow gastric emptying of glucose and decrease food intake in rats.Objective: We investigated the effects of intragastrically administered lysine on early (15 min) and later (60 min) blood glucose and insulin responses to and gastric emptying of a mixed-nutrient drink, and effects on subsequent energy intake.Methods: Twelve healthy volunteers (7 men and 5 women; mean ± SEM age: 24 ± 2 y) received intragastric infusions (200 mL) containing 5 or 10 g l-lysine or a control solution within 2 min on 3 different occasions in randomized order. Fifteen minutes later, participants consumed a mixed-nutrient drink (300 mL, 400 kcal, and 56 g carbohydrates) within 1 min. For the next hour (t = 0-60 min), we collected blood samples every 15 min (to measure blood glucose, plasma insulin, and plasma glucagon) and breath samples every 5 min (to measure gastric emptying via a 13C-acetate breath test). We then quantified subjects' energy intake from a buffet-style meal (t = 60-90 min).Results: There were no differences between the 2 lysine treatments; hence, data were pooled for further analysis. Lysine did not affect blood glucose at 15 min or the blood glucose area under the curve from 0 to 60 min (AUC0-60min) but it decreased blood glucose at 60 min compared with the control solution (-9.1% ± 3.1%, P < 0.01). Similarly, the early insulin response and insulin AUC0-60min were not affected by lysine, but plasma insulin at 60 min was 20.9% ± 5.6% lower than after the control (P < 0.05). Plasma glucagon at both 15 min (20.7% ± 4.7%, P < 0.001) and 60 min (14.1% ± 5.4%, P < 0.05) and the glucagon AUC0-60min (P < 0.01) were greater after lysine than after the control. Lysine did not slow gastric emptying, and there was no effect on energy intake.Conclusion: In healthy adults, lysine slightly reduced the glycemic response to an oral mixed-macronutrient drink, an effect that was apparently independent of insulin or slowing of gastric emptying. This trial was registered at www.anzctr.orgau as 12614000837628.