Effects of intraduodenal administration of quinine on blood glucose concentrations, gastric emptying, gut and gluco-regulatory hormone release, and gastrointestinal symptoms in healthy females.

Participants will receive in randomised, double-blind fashion, a 10-ml bolus of either (i) 600 mg quinine or (ii) 300 mg quinine, or (iii) water (control) intraduodenally on 3 separate visits. Visits will be scheduled during the follicular phase of the menstrual cycle (i.e., days 1-13) to minimise any potential effects of GI function. 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). 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 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, a baseline venous blood sample (10 mL) and Visual analogue Scale (VAS) questionnaire, to assess gastrointestinal symptoms (nausea and bloating), will be collected. Immediately thereafter (t = -31 min), participants will receive a 10-ml bolus of either (i) 600 mg quinine or (ii) 300 mg quinine, or (iii) water into the duodenum, after which the catheter will be removed and blood samples and VAS taken every 10 minutes. 30 min later (at t = -1 min), 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. Further venous blood samples and VAS will be taken every 10 min over the first 30 min after ingestion of the drink (t = 0 – 30 min) and then at 15-min intervals (t = 30 – 60 min), 30-min intervals (t = 60 – 120 min), and at t = 180 min. In addition, gastric emptying will be evaluated using breath test and 2D ultrasound (measuring antral area) at baseline and every 5 min after ingestion of the drink (t = 0 – 60 min) and then at 15-min intervals (t = 60 – 180 min). At t=180 min, after final blood and breath samples, ultrasound and VAS measurements, participants will be served a light lunch, after which they will be allowed to leave the laboratory