Effects of quinine, alone and combined with dietary nutrients, on gut function and blood glucose in healthy volunteers

Participants will receive in randomised, double-blind fashion, a 10-ml bolus of either (i) 600 mg quinine (ii) 300 mg quinine, (iii) water (control) intraduodenally on 3 separate visits. Each visit will be ~5 hours in duration, and separated by 3-7 days. In females, the study visits will be arranged in the 7-10 days from the start of their period cycle. Studies will be performed 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 ~13.5 hours overnight and refraining from alcohol and exercise for 24 hours, participants will arrive at the Clinical Research Facility by 8:15 am. Upon arrival, participants will be given a standardised light breakfast (1 slice (30 g) white bread, 10 g jam and a cup (200 ml) black tea; ~100 kcal), after which they 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 infusion port will be positioned ~ 14 cm distal to the pylorus. The correct positioning of the catheter will be monitored continuously by measurement of the transmucosal potential difference in the stomach (~ -40 mV) and the duodenum (~ 0 mV). Once the catheter has been positioned correctly, an intravenous cannula will be placed into a forearm vein for regular blood sampling. At 11.30 am, t = -30 min, a baseline blood sample (10 ml) will be taken, the participant will complete a validated 100-ml Visual Analogue Scale (VAS) questionnaire to assess appetite-related perceptions and gastrointestinal (GI) symptoms as well as the Leeds Food Preference Questionnaire, which is a computerised behavioural task that provides measures of 'liking' and 'wanting' components of food preference and food reward. Immediately thereafter (t = -30 min), participants will receive either (i) 600 mg quinine, (ii) 300 mg quinine, (iii) water into the duodenum. 10-ml blood samples for the measurement of plasma concentrations of hormones and glucose will be collected every 10 min (-20, -10, 0), and participants complete VAS questionnaires. Participants will complete Leeds Food Preference Questionnaire once immediately before quinine administration (t=-30) and once 30 minutes later, immediately before the buffet meal (t=-1). Participants will be presented with the buffet meal (t=0) which comprises of 4 slices (~120 g) of whole-meal bread, 4 slices (~120 g) of white bread, 100 g sliced ham, 100 g sliced chicken, 85 g sliced cheddar cheese, 100 g lettuce, 100 g sliced tomato, 100 g sliced cucumber, 22 g mayonnaise, 20 g margarine, 1 apple (~170 g), 1 banana (~190 g), 175 g vanilla yogurt, 100 g chocolate custard, 120 g fruit salad, 375 mL iced coffee, 300 mL orange juice, and 600 mL water and has a total energy content of ~2300 kcal (~27% fat, ~52% carbohydrate, and ~21% protein) and weight of ~2924. Participants will be allowed 30 min to freely consume the meal until comfortably full. Immediately after the meal (t = 30 min) and then every 30 min (t = 60 and 90 min), blood samples will be collected and participants complete VAS questionnaires. At t = 90 min, the intravenous cannula will be removed, and participants will be allowed to leave the laboratory.