Effects of Intragastric Quinine, Alone or Combined With L-leucine, on Postprandial Glycaemic Control

In this study, participants will receive, in a randomized, double-blind fashion, an intragastric bolus administration of either (i) 300 mg quinine, (ii) 5 g L-leucine, (iii) a combination of (i)+(ii), or (iv) control, before 350 ml (500 kcal) of a mixed-nutrient drink, to evaluate the effects on postprandial blood glucose, gastric emptying, and the hormone, and appetite, responses to the mixed-nutrient drink. Study visits will be separated by 3-7 days and participants will receive one treatment per visit.On each study visit, the participant will be intubated with a nasogastric feeding tube. At t= - 60 min (08:30 am), a baseline blood sample, visual analogue scale questionnaire (VAS), and breath sample will be collected and quinine or control will be administered through the feeding tube. 30 min later (at t= - 30 min), L-leucine or control will be administered over 2 min after which the feeding tube will be removed immediately. At t = -45, -30, -15, and -1 min further blood samples will be collected and VAS completed. At t = -1 min, participants will consume, within 1 minute, a mixed-nutrient drink, labelled with 100 mg of 1-13C-acetate for measurement of gastric emptying by breath sampling. Blood samples, VAS, and breath samples will be taken at regular intervals between t = 0-180 min.

Inclusion Criteria:Lean weight (BMI 19-25 kg/m2)Exclusion Criteria:Significant gastrointestinal symptoms, disease or surgery;Current gallbladder or pancreatic disease;Cardiovascular or respiratory diseases;Any other illnesses as assessed by the investigator (including chronic illnesses not explicitly listed above);Use of prescribed or non-prescribed medications (including vitamins and herbal supplements) which may affect energy metabolism, gastrointestinal function, bodyweight or appetite (eg domperidone and cisapride, anticholinergic drugs (eg atropine), metoclopramide, erythromycin, hyoscine, orlistat, green tea extracts, Astragalus, St Johns Wort etc.);Individuals with low ferritin levels (less than 30 ng/mL), or who have donated blood in the 12 weeks prior to taking part in the study;Lactose intolerance/other food allergy(ies);Vegetarians;Restrained eaters (score >12 on the three-factor eating questionnaire);Current intake of greater than 2 standard drinks on greater than 5 days per week;Current smokers of cigarettes/cigars/marijuana;Current intake of any illicit substance;High performance athletes;Inability to comprehend study protocol;Unable to tolerate naso-gastric tube