Effects of small intestinal L-valine on gut function, gut hormone release and blood glucose control in healthy, lean volunteers.

The intervention in this study consists of the intraduodenal infusion of an L-valine or control solution over a 90 minute period during which the measurement of gut motility, blood glucose, gut hormone concentration, insulin concentrations, appetite perceptions and energy intake during a buffet meal will be measured. Subjects enrolled into the study will receive, in randomized, double-blind fashion (i) 0.15 kcal/min L-valine, (ii) 0.45 kcal/min L-valine, (iii) saline (control), each occurring at separate visits. Each visit will last 3-6hrs in duration, and will be separated by 3-7 days. Visits will be carried out in the clinic room facility of the Discipline of Medicine, University of Adelaide by staff members trained in the required techniques, and will be conducted on an individual basis. Subjects will be asked to consume a standardised dinner meal the night before each visit by no later than 6pm, After fasting for 14 hrs overnight and refraining from exercise and alcohol for 24 hrs, subjects will arrive at the laboratory at 8am . Upon arrival, subjects will be intubated with a 17-channel manometric catheter that will be inserted through an anaesthetised nostril and allowed to pass through the stomach and into the duodenum by peristalsis. The manometric catheter consists of 16 side holes spaced at 1.5 cm intervals, measuring pressures in the antrum, pylorus, and duodenum (APD pressures). An additional channel (with the side hole positioned approx 14 cm distal to the pylorus when the catheter is in position) is used for intraduodenal infusions. The correct positioning of the catheter will be maintained by continuous measurement of the transmucosal potential difference (TMPD) between the most distal antral channel and the most proximal duodenal channel. All manometric channels will be perfused with degassed, distilled water, except for the two TMPD channels, which will be perfused with degassed 0.9% saline, at 0.15 ml/min. An intravenous cannula will be placed into a right forearm vein for regular blood sampling to measure plasma hormone concentrations and blood glucose. Once the catheter has been positioned correctly, fasting motility will be monitored continuously, and immediately after the end of phase III activity of the fasting migrating motor complex (MMC), during a period of motor quiescence (t=-15 - 0 min), a 12 ml venous blood sample (baseline) will be taken, and the subject will complete a visual analogue scale questionnaire (VAS) to assess appetite-related perceptions (fullness, hunger, etc.) and gastrointestinal symptoms (nausea and bloating). At t = 0 min (during phase I of the MMC), the 90-min intraduodenal infusion (either (i), (ii), or (iii) as outlined above) will commence . APD pressures will be measured continually over the 90-min period. Blood samples will be collected and VASs completed every 15 min from t = 0 to 90 min. At t = 90 min, the manometric catheter will be removed and subjects will be presented with a cold, buffet-style meal. Subjects will be allowed 30 min to freely consume food until they are comfortably full. At t = 120 min, a final blood sample will be taken, and VAS administered. The intravenous cannula will then be removed and subjects will be allowed to leave the laboratory. A total of 96 ml of blood will be taken on each study day (288 ml over all study visits).