The metabolic effects of bitter taste sensing in the gut

INTERVENTION: Following a screening visit, each subject will be studied on 5 occasions, separated by at least 7 days, in a double‐blinded randomised order. On each study day, an intravenous cannula will be inserted into a forearm vein for repeated blood sampling. The subject will then be positioned in the left lateral decubitus position, and the 20mL aqueous gel (1% carboxymethyl cellulose) containing DB (30mg), DB (30mg) + probenecid (456mg), TCA (3500mg), TCA (3500mg) + probenecid (456mg), or vehicle only, will be infused into the rectum via a soft catheter by a medically qualified investigator within 2 min and then be removed. CONDITION: Type 2 diabetes mellitus obesity PRIMARY OUTCOME: differences in the incremental area under the curve (iAUC) for plasma GLP‐1 between the 5 treatments. SECONDARY OUTCOME: differences in energy intake from a standardised cold buffet meal between the 5 treatments. differences in the incremental area under the curve (iAUC) for gastrointestinal sensations, assessed by validated visual analogue scales, between the 5 treatments. differences in the incremental area under the curve (iAUC) for plasma glucose between the 5 treatments. differences in the incremental area under the curve (iAUC) for plasma PYY between the 5 treatments. INCLUSION CRITERIA: Healthy male and females aged 18 – 55 years Body mass index (BMI) 19 ‐ 25 kg/m2 Haemoglobin above the lower limit of the normal range (ie. >135g/L for men and 115g/L for women), and ferritin above the lower limit of normal (ie. >30ng/mL for men and >20mg/mL for women)