Effects of combined administration of L-tryptophan and lauric acid on gut functions, and blood glucose control in healthy humans

INTERVENTION: We will investigate the effects of a combination of intraduodenally administered L‐tryptophan and lauric acid on gut motor functions (including antropyloroduodenal motility and gastric emptying), gut hormone release and blood glucose in response to a mixed‐nutrient drink in healthy volunteers. Each volunteer will be studied on four occasions, separated by at least 3 (and up to 7) days. On each occasion, participants will receive, in randomised, double‐blind fashion, a 45‐min intraduodenal infusion of: (i) L‐tryptophan at 0.10 kcal/min (1.1 g/45 min), (ii) lauric acid at 0.3 kcal/min (1.5 g/45 min), (iii) combination of (i) and (ii), or (iv) saline (control) On each study occasion, participants will attend the laboratory at 08:00 hr, after fasting overnight, and will be intubated, via an anaesthetised nostril, with a small‐diameter nasoduodenal manometric catheter consisting of 16 channels plus an infusion port. The catheter will be allowed to pass through the stomach and into the duodenum. Once the catheter is positioned correctly, with the sleeve sensor straddling the pylorus, fasting motility will be observed until a phase III of the interdigestive migrating motor complex occurs. Immediately following the cessation of phase III, and during phase I, an intravenous cannula will be inserted for blood sampling (to measure gut hormones and blood glucose). At t = ‐10 min, participants will complete a VAS questionnaire, then at t = 0 min, a baseline blood sample and breath sample (to measure gastric emptying), will be taken, and participants will complete another VAS questionnaire. At t = 0 min, the infusion will commence, and continue until t = 45 min. At t = 30 min, participants will be given a mixed‐nutrient drink (containing 500 kcal, 74 g carbohydrates) to consume within 2 min, which will be marked with carbon‐13 acetate to facilitate the measurement of gastric emptying using 13C‐breath test. ‐ Blood samples will be taken a CONDITION: Diet and Nutrition ‐ Obesity Metabolic and Endocrine ‐ Diabetes Oral and Gastrointestinal ‐ Normal oral and gastrointestinal development and function Type 2 diabetes;Obesity;Healthy Human Gastrointestinal Physiology ; ; Type 2 diabetes ; Obesity ; Healthy Human Gastrointestinal Physiology PRIMARY OUTCOME: Changes in C‐peptide, and other gut hormone concentrations, including cholecystokinin, GLP‐1 and GIP, This outcome is of an exploratory nature so that other gut hormones to be measured may be decided upon based on the effects of this intervention on plasma glucose, and other outcomes. [Plasma will be obtained from blood samples taken at t = 0, 15, 30, 40 , 50, 60, 75, 90, 120, and 150 min.] Changes in plasma glucose concentration[Plasma will be obtained from blood samples taken at t = 0, 15, 30, 40 , 50, 60, 75, 90, 120, and 150 min.] Gastric emptying will be measured using breath samples [Breath samples will be collected at t = ‐10, 30, 35. 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, and 210 min.] SECONDARY OUTCOME: Antropyloroduodenal motility measured by nasoduodenal manometric catheter[Continuous measurement from t = ‐ 10 to 150 min. ] Desire to eat will be measured using a VAS questionnaire ; [VAS questionnaires will be completed at t = ‐10, 0, 15, 30, 40 , 50, 60, 75, 90, 105, 120, 135 and 150 min.] Fullness sensation will be measured using a VAS questionnaire ; [VAS questionnaires will be completed at t = ‐10, 0, 15, 30, 40 , 50, 60, 75, 90, 105, 120, 135 and 150 min.] Hunger sensation will be measured using a VAS questionnaire INCLUSION CRITERIA: Healthy lean (BMI 19 ‐ 25 kg/m2) male volunteers aged between 18‐55 years, non‐smokers, and without significant illness will be included in the study. ; [VAS questionnaires will be completed at t = ‐10, 0, 15, 30, 40 , 50, 60, 75, 90, 105, 120, 135 and 150 min.] Nausea will be measured using a VAS questionnaire [VAS questionnaires will be completed at t = ‐10, 0, 15, 30, 40 , 50, 60, 75, 90, 105, 120, 135 and 150 min.] Prospective consumption will be measured using a VAS questionnaire[VAS questionnaires will be completed at t = ‐10, 0, 15, 30, 40 , 50, 60, 75, 90, 105, 120, 135 and 150 min.]