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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Taste Disorder, Primary, Sweet

Intervention / Treatment
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* Dietary Supplement: lactisole
* Other: mixed liquid meal


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: glucose<br>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) | Dietary Supplement: lactisole<br>* flavoring agent/sweet taste antagonist<br>* Other names: Dietary supplement;|
| Active Comparator: glucose + lactisole<br>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 | Dietary Supplement: lactisole<br>* flavoring agent/sweet taste antagonist<br>* Other names: Dietary supplement;|
| Active Comparator: mixed liquid meal<br>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) | Other: mixed liquid meal<br>* Ensure Plus<br>* Other names: Dietary supplement;|
| Active Comparator: mixed liquid meal + lactisole<br>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 | Other: mixed liquid meal<br>* Ensure Plus<br>* Other names: Dietary supplement;|
| Placebo Comparator: saline + lactisole<br>saline (0.9 %; rate: 2.5 mL/min for 180 min) + 450 ppm lactisole | Dietary Supplement: lactisole<br>* flavoring agent/sweet taste antagonist<br>* Other names: Dietary supplement;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gastrointestinal peptide secretion | Assessment of venous GLP-1 and PYY release to meal stimulation with and without sweet receptor blockade | 4 hours blood sampling | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Appetite perceptions during 4 hours using VAS | Assessment of the following appetite perception markers: feelings of hunger, feelings of fullness, feelings of satiety using validated visual analogue scales | 4 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T1R2/T1R3, gastric emptying, gut, lactisole, nutrient sensing