Role of the Gut Sweet Taste Receptor in the Secretion of Glucagon-like Peptide-1 and Peptide YY

The Role of Sweet Taste Receptor Blockade on Intraduodenal Glucose- and Liquid Meal-stimulated Secretion of Satiation Peptides in Healthy Humans

The purpose of this study is to determine the functional significance of sweet taste receptors in the secretion of GI satiation peptides by using a specific sweet taste receptor antagonist to block sweet taste perception in the gastrointestinal tract.

There is strong evidence that taste signaling mechanisms identified in the oral epithelium also operate in the gut. It is suggested that open-type enteroendocrine cells directly sense nutrient via alpha-gustducin coupled taste receptors to modulate the secretion of glucagon like peptide-1 (GLP-1) and peptide YY (PYY). Several nutrient responsive G-protein coupled receptors have been identified in the human gut, including the sweet taste responsive T1R2/T1R3 heterodimer, the amino acid/umami responsive T1R1/T1R3 as well as GPR120 for unsaturated long-chain free fatty acids.The functional significance of sweet taste receptors in the secretion of GLP-1 and PYY will be determined by intraduodenal perfusion of glucose (I) or a mixed liquid meal (II) with or without lactisole (450 ppm) in a double blind, 5-way crossover trial including 10 healthy subjects.

intraduodenal perfusion of glucose (29.3 g glucose per 100 mL; rate: 2.5 mL/min for 180 min; caloric load: 3.0 kcal/min)

intraduodenal perfusion of glucose (29.3 g glucose per 100 mL; rate: 2.5 mL/min for 180 min; caloric load: 3.0 kcal/min) + 450 ppm lactisole

intraduodenal perfusion of a mixed liquid meal (20.20 g carbohydrate, 4.92 g fat and 6.25 g protein per 100 mL; rate: 2.5 mL/min for 180 min; caloric load: 3.0 kcal/min)

intraduodenal perfusion of a mixed liquid meal (20.20 g carbohydrate, 4.92 g fat and 6.25 g protein per 100 mL; rate: 2.5 mL/min for 180 min; caloric load: 3.0 kcal/min) + 450 ppm lactisole

Assessment of venous GLP-1 and PYY release to meal stimulation with and without sweet receptor blockade

Assessment of the following appetite perception markers: feelings of hunger, feelings of fullness, feelings of satiety using validated visual analogue scales

Inclusion Criteria: Healthy subjects BMI of 19.0-24.5 Age 18-40 stable body weight for at least 3 month Exclusion Criteria: smoking substance abuse regular intake of medication medical or psychiatric illness gastrointestinal disorders or food allergies

Steinert RE, Meyer-Gerspach AC, Beglinger C. The role of the stomach in the control of appetite and the secretion of satiation peptides. Am J Physiol Endocrinol Metab. 2012 Mar 15;302(6):E666-73. doi: 10.1152/ajpendo.00457.2011. Epub 2012 Jan 3.

Steinert RE, Gerspach AC, Gutmann H, Asarian L, Drewe J, Beglinger C. The functional involvement of gut-expressed sweet taste receptors in glucose-stimulated secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). Clin Nutr. 2011 Aug;30(4):524-32. doi: 10.1016/j.clnu.2011.01.007. Epub 2011 Feb 15.