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

INTERVENTION: 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 p CONDITION: Diet and Nutrition ‐ Obesity Metabolic and Endocrine ‐ Diabetes Oral and Gastrointestinal ‐ Normal oral and gastrointestinal development and function Type 2 diabetes;Obesity;Healthy human gastrointestinal physiology; ; Type 2 diabetes ; Obesity ; Healthy human gastrointestinal physiology PRIMARY OUTCOME: Blood glucose concentrations before and after quinine or control administration, and following the mixed nutrient drink.[Blood glucose will be assessed from venous blood samples taken at baseline, every 10 minutes in response to quinine or control, and then at regular time points for 3 hours following the mixed‐nutrient drink.] SECONDARY OUTCOME: Gastric emptying (measurement of 13CO2 in breath samples and by measuring antral area with 2D Ultrasound).[Breath samples will be collected and 2D Ultrasound measurements will be performed at baseline, and then every 5 minutes for the first hour, and every 15 minutes for the next two hours after the mixed‐nutrient drink.] Gastrointestinal symptoms (nausea, bloating) will be measured using a 100mm Visual Analogue Scale (VAS) questionnaire. This is a composite outcome. ; [Gastrointestinal symptoms will be assessed at baseline, every 10 minutes in response to quinine or control, and then at regular time points for 3 hours following the mixed‐nutrient drink.] Plasma concentrations of gluco‐regulatory and gut hormones (e.g. insulin, glucagon, GLP‐1). This outcome is of an exploratory nature so that the specific 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.[Plasma hormone concentrations will be assessed from venous blood samples taken at baseline, every 10 minutes in response to quinine or control, and then at regular time points for 3 hours following the mixed‐nutrient drink.] INCLUSION CRITERIA: Healthy Lean weight (BMI 19‐25 kg/m2)