Effects of intraduodenal versus intragastric administration of quinine on blood glucose and gut function in healthy, lean volunteers.

Participants will receive in randomised, double-blind fashion, a bolus of either quinine (600mg), or water (total volume: 10mL), either intraduodenally or intragastrically on 4 separate visits. Each visit will be ~5hrs in duration, and separated by 3-7 days. Visits will be carried out at the Clinical Research Facility, Adelaide Medical School, University of Adelaide, by staff and students trained in the required clinical research techniques. Participants will consume a standardised dinner meal, (400g McCain's beef lasagne), the night before each study visit by no later than 7pm. After fasting for 14 hours overnight and refraining from alcohol and exercise for 24 hours, participants will arrive at the Clinical Research Facility by 8:30am. Upon arrival, participants will be intubated with a 17-channel manometric catheter (Dentsleeve, Mui Scientific) 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). The most proximal antral channel (with the side hole positioned approximately 9cm proximal to the pylorus when the catheter is in position) is used for intragastric administration. An additional channel (with the side hole positioned approximately 14 cm distal to the pylorus when the catheter is in position) is used for intraduodenal administration. 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. 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, an 8 ml venous blood sample (baseline) will be taken, and the subject will complete a 100mm visual analogue scale questionnaire (VAS) to assess GI symptoms (nausea and bloating). Either the intraduodenal (t = -32) or intragastric (t=- 62) bolus of quinine or water will be administered and the manometric catheter was then removed, after which venous blood samples and VAS taken every 10 minutes. 30 min after intraduodenal infusion and 60 min after intragastric infusion, (at t = -1), participants will consume, within 1 minute, 350ml (500 kcal) of a mixed-nutrient drink (Resource Plus) labelled with 100mg of 13C-acetate for measurement of gastric emptying by breath sampling. Regular venous blood samples and VAS will be taken throughout the study and breath samples taken every 5 minutes for the first hour after the drink (t= 0 – 60 min) and every 15 minutes for the second hour (t= 60 – 120 min).