Effects of Intragastric Administration of Tryptophan on the Blood Glucose Response to a Nutrient Drink and Energy Intake, in Lean and Obese Men

Abstract

Tryptophan stimulates plasma cholecystokinin and pyloric pressures, both of which slow gastric emptying. Gastric emptying regulates postprandial blood glucose. Tryptophan has been reported to decrease energy intake. We investigated the effects of intragastric tryptophan on the glycaemic response to, and gastric emptying of, a mixed-nutrient drink, and subsequent energy intake. Lean and obese participants (n = 16 each) received intragastric infusions of 1.5 g (“Trp-1.5g”) or 3.0 g (“Trp-3.0g”) tryptophan, or control, and 15 min later consumed a mixed-nutrient drink (56 g carbohydrates). Gastric emptying (13C-acetate breath-test), blood glucose, plasma C-peptide, glucagon, cholecystokinin and tryptophan concentrations were measured (t = 0–60 min). Energy intake was assessed between t = 60–90 min. In lean individuals, Trp-3.0g, but not Trp-1.5g, slowed gastric emptying, reduced C-peptideAUC and increased glucagonAUC (all P < 0.05), but did not significantly decrease the blood glucose response to the drink, stimulate cholecystokinin or reduce mean energy intake, compared with control. In obese individuals, Trp-3.0g, but not Trp-1.5g, tended to slow gastric emptying (P = 0.091), did not affect C-peptideAUC, increased glucagonAUC (P < 0.001) and lowered blood glucose at t = 30 min (P < 0.05), and did not affect cholecystokinin or mean energy intake. In obese individuals, intragastrically administered tryptophan may reduce postprandial blood glucose by slowing gastric emptying; the lack of effect on mean energy intake requires further investigation.

Plasma Free Amino Acid Responses to Whey Protein and Their Relationships with Gastric Emptying, Blood Glucose- and Appetite-Regulatory Hormones and Energy Intake in Lean Healthy Men

“…In contrast to the aforementioned studies, a strength of the current design was that we measured all 20 AAs and, thereby, could evaluate the interplay between these AAs and how they collectively influence glucose- and appetite-regulatory hormones, as well as energy intake. As such, the current study extends current knowledge [13,14,15,16,34,35,36,37,38] by demonstrating that leucine, valine, isoleucine, methionine and lysine (all essential AAs) and tyrosine (conditionally-essential AA) are each associated strongly with postprandial concentrations of CCK, GLP-1, insulin and glucagon, to a lesser extent with ghrelin, and weakly with protein-induced suppression of energy intake.…”

“…Evidence for differential roles of specific AAs in the regulation of glucose- and appetite-regulatory hormones, and the suppression of energy intake, is derived from studies in both animals [32,33] and humans [34,35,36,37,38]. In healthy men, we have reported previously that leucine [34], but not valine [35], each infused ID at a rate of 0.45 kcal/min for 90 min, modulated gut motor and hormone functions, blood glucose and/or energy intake.…”

“…We also found that intragastric administration of lysine (at loads of 5 and 10 g) reduced the glycaemic response to a mixed-nutrient drink moderately [36]. Moreover, in lean and obese individuals, intragastric administration of 3 g of tryptophan slowed gastric emptying and increased glucagon, but did not suppress subsequent energy intake substantially [37], whereas a solution containing 3.3 g tryptophan infused ID at a rate of 0.15 kcal/min for 90 min, stimulated pyloric pressures, the release of CCK, and to a lesser extent, GLP-1 and PYY, and significantly reduced energy intake by ~200 kcal [38]. In contrast to the aforementioned studies, a strength of the current design was that we measured all 20 AAs and, thereby, could evaluate the interplay between these AAs and how they collectively influence glucose- and appetite-regulatory hormones, as well as energy intake.…”

The aromatic amino acid sensor GPR142 controls metabolism through balanced regulation of pancreatic and gut hormones

“…This inhibitory effect of the GPR142 agonist on gastric emptying, which probably mainly is mediated by CCK, could relate to a possible physiological role of GPR142 being one of several sensors of dietary protein ingestion as gastric emptying plays an important role in controlling delivery of protein for further digestion and absorption in the small intestine. Interestingly, gastric emptying is reduced by oral tryptophan in humans [36], [37], which very well could be mediated through GPR142. The effect on gastric emptying should be taken into account when evaluating the therapeutic potential of GPR142 agonist.…”

Gastrointestinal Sensing of Meal-Related Signals in Humans, and Dysregulations in Eating-Related Disorders

“…The role of specific amino acids in the responses to protein is currently unclear, with limited information on the comparative effects of amino acids on GI functions and energy intake in health and obesity. Intraduodenal infusion of tryptophan had comparable effects on pyloroduodenal motility in lean and overweight participants [113], and intragastrically administered tryptophan slowed gastric emptying and reduced energy intake after a mixed-nutrient drink in ~50% of lean and obese individuals [114]. In contrast, obese individuals have been reported to be less able to detect glutamate orally [115], suggesting that obese individuals may be less sensitive to palatable umami taste, which may contribute to higher food intakes.…”