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

INTERVENTION: Subjects will receive in randomised, double‐blind fashion, a 600mg bolus administration of quinine either intraduodenally or intragastrically on 2 separate visits. Each visit will last 5hrs in duration, and will be separated by 3‐7 days. Visits will be carried out in the Adelaide Medical School, University of Adelaide, by staff members trained in the required clinical research facilities. Subjects will consume a standardised dinner meal, a 400g McCain's beef lasagne, the night before both study visits by no later than 7pm. After fasting for 14 hours overnight and refraining from alcohol and exercise for 24 hours, subjects will arrive at the clinical research facility by 8:30am. Upon arrival, subjects 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 corr CONDITION: Diet and Nutrition ‐ Obesity Metabolic and Endocrine ‐ Diabetes Obesity;Type 2 Diabetes;Healthy human gastrointestinal physiology; ; Obesity ; Type 2 Diabetes ; Healthy human gastrointestinal physiology Oral and Gastrointestinal ‐ Normal oral and gastrointestinal development and function INCLUSION CRITERIA: Healthy Lean weight (BMI 19‐25 kg/m2) PRIMARY OUTCOME: Antropyloroduodenal motility (number of antral, duodenal and isolated pyloric pressure waves, and basal pyloric pressure) will be measured using a 17‐channel manometric assembly (Dentsleeve, Mui Scientific).; This outcome is of an exploratory nature so that specific motility parameters to be measured may be decided upon based on the effect of the intervention on this and other outcomes, therefore, this is a composite outcome.[Baseline (t = ‐10 ‐ 0) and after administration (t = 0 ‐120). ] Plasma concentrations of gluco‐regulatory and gut hormones (Insulin, GLP‐1, CCK, glucagon, ghrelin, PYY). ; This outcome is of an exploratory nature so that specific gastrointestinal hormones to be measured may be decided upon based on the effect of the intervention on this and other outcomes, therefore, this is a composite outcome.[Samples will be collected at t = ‐10, 0 , 10, 20 , 30 , 45, 60 , 75 , 90, 120 min, where t = ‐10 is prior to quinine administration and t = 0 is immediately post‐administartion. ] SECONDARY OUTCOME: Blood glucose concentrations.[Samples will be collected at t = ‐10, 0 , 10, 20 , 30 , 45, 60 , 75 , 90, 120 min.] Measure bloating using a 100mm visual analogue scale questionnaire. [Data will be collected at t = ‐10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.] Measure desire to eat using a 100mm visual analogue scale questionnaire. [Data will be collected at t = ‐10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.] Measure fullness using a 100mm visual analogue scale questionnaire. [Data will be collected at t = ‐10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.] Measure hunger using a 100mm visual analogue scale questionnaire. [Data will be collected at t = ‐10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.] Measure nausea using a 100mm visual analogue scale questionnaire. [Data will be collected at t = ‐10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.] Measure satiety using a 100mm visual analogue scale questionnaire. [Data will be collected at t = ‐10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.] Measure the amount of food the subjects thinks they can eat to eat using a 100mm visual analogue scale questionnaire. [Data will be collected at t = ‐10, 0, 10, 20, 30 ,45, 60, 75, 90, 105, 120 min.]