Abstract

In humans, phenylalanine stimulates plasma cholecystokinin (CCK) and pyloric pressures, both of which are important in the regulation of energy intake and gastric emptying. Gastric emptying is a key determinant of postprandial blood glucose. We evaluated the effects of intragastric phenylalanine on appetite perceptions and subsequent energy intake, and the glycaemic response to, and gastric emptying of, a mixed-nutrient drink. The study consisted of two parts, each including 16 healthy, lean males (age: 23 ± 1 years). In each part, participants received on three separate occasions, in randomised, double-blind fashion, 5 g (Phe-5 g) or 10g (‘Phe-10 g) L-phenylalanine, or control, intragastrically, 30 min before a standardised buffet-meal (part A), or a standardised mixed-nutrient drink (part B). In part A, plasma CCK and peptide-YY (PYY), and appetite perceptions, were measured at baseline, after phenylalanine alone, and following the buffet-meal, from which energy intake was assessed. In part B, plasma glucose, glucagon-like peptide-1 (GLP-1), insulin and glucagon were measured at baseline, after phenylalanine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured by 13C-acetate breath-test. Phe-10 g, but not Phe-5 g, stimulated plasma CCK (p = 0.01) and suppressed energy intake (p = 0.012); energy intake was correlated with stimulation of CCK (r = −0.4, p = 0.027), and tended to be associated with stimulation of PYY (r = −0.31, p = 0.082). Both Phe-10 g and Phe-5 g stimulated insulin and glucagon (all p < 0.05), but not GLP-1. Phe-10 g, but not Phe-5 g, reduced overall plasma glucose (p = 0.043) and peak plasma glucose (p = 0.017) in response to the mixed-nutrient drink. Phenylalanine had no effect on gastric emptying of the drink. In conclusion, our observations indicate that the energy intake-suppressant effect of phenylalanine is related to the stimulation of CCK and PYY, while the glucoregulatory effect may be independent of stimulation of plasma GLP-1 or slowing of gastric emptying.

Highlights

  • Nutrient sensing in the small intestinal lumen is critical to the release of gut and gluco-regulatory hormones, including cholecystokinin (CCK), released predominantly in the proximal small intestine, Nutrients 2020, 12, 1788; doi:10.3390/nu12061788 www.mdpi.com/journal/nutrientsNutrients 2020, 12, 1788 and peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), in the distal small intestine [1].These hormones mediate nutrient-induced slowing of gastric emptying, and the suppression of energy intake and postprandial blood glucose [1,2,3]

  • Because relatively large amounts of protein are required for these effects, there has been an interest in characterising the effects of amino acids on upper gut functions, energy intake and postprandial blood glucose control, since amino acids are likely to mediate these effects of protein

  • The findings from this study add to a growing body of evidence that a number of amino acids have effects to reduce energy intake and/or postprandial blood glucose in humans, at least in part, by stimulating the release of gut and/or pancreatic hormones, and some amino acids by slowing gastric emptying [9,10,11,18,20,21,36,37,38]

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Summary

Introduction

Nutrients 2020, 12, 1788 and peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), in the distal small intestine [1]. These hormones mediate nutrient-induced slowing of gastric emptying, and the suppression of energy intake and postprandial blood glucose [1,2,3]. Whey protein, when administered intraduodenally or consumed 30 min before a meal, reduce energy intake and postprandial blood glucose, at least in part, by slowing gastric emptying and stimulating hormones, including CCK, PYY and GLP-1 [6,7,8]. Because relatively large amounts of protein (up to 55 g, or 226 kcal) are required for these effects, there has been an interest in characterising the effects of amino acids on upper gut functions, energy intake and postprandial blood glucose control, since amino acids are likely to mediate these effects of protein

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