SEGATROM: Sensory and Gastrointestinal Impact of Taste Receptor Variants on Human Metabolism and Nutrition

Study Overview
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Brief Summary
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We investigate the impact of taste receptors (sweet, bitter and umami) on human metabolism. There ist growing evidence, that components of the taste signalling system, including the taste receptor proteins , have important functions in the regulation of metabolic parameters in non-gustatory tissues.

Detailed Description
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We apply different sweet, bitter and umami taste compounds in a single dose in the human intervention. We use substances as for instance glucose, sucrose,saccharin and lactisol in the sweet part, and substances from cabbage, beer or red endive in the bitter part. For umami we take glutamate. Blood samples are collected at baseline and 6 times thereafter up to 3hours, to analyse the incretins GLP-1(glucagon-like peptide 1) and GIP(gastrointestinal polypeptide) and other peptide hormones as insulin and PYY(peptide tyrosin trosin) in human beings. Gastrointestinal mucosa is taken by gastroscopy from the lower duodenum from study subjects for analysis for the presence or absence of functional taste receptors in gastrointestinal tissues.

Official Title
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Sensory and Gastrointestinal Impact of Taste Receptor Variants on Human Metabolism and Nutrition

Conditions
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Disorder of Glucose Regulation

Intervention / Treatment
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* Dietary Supplement: sweet block
* Dietary Supplement: bitter block
* Dietary Supplement: umami-block
* Other: gastroscopy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy persons Exclusion Criteria: Tumor in history Pregnancy Severe illness in history Bodymass index below 18

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sweet -block<br>application of different sugars, artificial sweeteners and sweet-taste antagonists in a single dose in 300 ml tap water every week up to 7 times and collection of blood samples over 3 hours | Dietary Supplement: sweet block<br>* oral application of the above mentioned substances in 300 ml tap water in 5 min. , collection of blood at 0,15,30, 60 ,120,180 minutes for measurement of incretins GIP(gastrointestinal polypeptide) and GLP-1 (glucagon like peptide 1), Protein hormones PYY(Peptide YY),CCK (cholecystokinin), Leptin and Insulin<br>* Other names: sweet taste antagonist as lactisol;Dietary Supplement: bitter block<br>* oral application of the above mentioned substances in 300 ml tap water, collection of blood samples at -15,0,15,30,60,120,180 min for Insulin, GIP,GLP-1, PYY and glucose<br>* Other names: iso-alpha-acid;Dietary Supplement: umami-block<br>* oral application of umami substances as glutamate with and without IMP, collection of blood samples as above<br>* Other names: application of glutamate and glutamate+IMP,;|
| Experimental: bitter block<br>application of purified bitter tasting ingredients of vegetables and hop in 300 ml tap water , collection of blood samples for 3h (-15,0,15,30,60,120,180 min) | Dietary Supplement: sweet block<br>* oral application of the above mentioned substances in 300 ml tap water in 5 min. , collection of blood at 0,15,30, 60 ,120,180 minutes for measurement of incretins GIP(gastrointestinal polypeptide) and GLP-1 (glucagon like peptide 1), Protein hormones PYY(Peptide YY),CCK (cholecystokinin), Leptin and Insulin<br>* Other names: sweet taste antagonist as lactisol;Dietary Supplement: bitter block<br>* oral application of the above mentioned substances in 300 ml tap water, collection of blood samples at -15,0,15,30,60,120,180 min for Insulin, GIP,GLP-1, PYY and glucose<br>* Other names: iso-alpha-acid;Dietary Supplement: umami-block<br>* oral application of umami substances as glutamate with and without IMP, collection of blood samples as above<br>* Other names: application of glutamate and glutamate+IMP,;|
| Experimental: umami-block<br>application of glutamate and glutamate +IMP same procedure as above | Dietary Supplement: sweet block<br>* oral application of the above mentioned substances in 300 ml tap water in 5 min. , collection of blood at 0,15,30, 60 ,120,180 minutes for measurement of incretins GIP(gastrointestinal polypeptide) and GLP-1 (glucagon like peptide 1), Protein hormones PYY(Peptide YY),CCK (cholecystokinin), Leptin and Insulin<br>* Other names: sweet taste antagonist as lactisol;Dietary Supplement: bitter block<br>* oral application of the above mentioned substances in 300 ml tap water, collection of blood samples at -15,0,15,30,60,120,180 min for Insulin, GIP,GLP-1, PYY and glucose<br>* Other names: iso-alpha-acid;Dietary Supplement: umami-block<br>* oral application of umami substances as glutamate with and without IMP, collection of blood samples as above<br>* Other names: application of glutamate and glutamate+IMP,;|
| Other: gastroscopy<br>gastroscopy with and without oral intervention with artificial sweetener saccharin to take tissue samples from the upper bowel for the investigation of taste receptor cells in the upper bowel in human beings | Other: gastroscopy<br>* gastroscopy with and without oral application of saccharin, tissue samples from th upper duodenum by endoscopy for the detection of taste receptor cells in the upper bowel<br>* Other names: SGLT-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the curve (AUC): changes of expression levels of the sweet , bitter und umami taste receptors in humans in the upper bowel and responses of incretins to receptor agonists and antagonists | measurement of incretins (GIP, GLP-1) and peptide hormones in human plasma after consumption of different sugars , sweeteners , bitter tasting ingredients of vegetables und umami. Measurement of expression levels in human intestinal mucosa before and after receptor stimulation | three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes in the signalling cascade of the sweet receptor SGLT1 (sodium tranporter 1), changes of receptor expression | oral application of sweet tasting substances and antagonists, endoscopic collection of tissue samples, determination of molecular resonses by qRT-PCR and immunohistochemistry | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SGLT1 (sodium dependent glucose transporter), Glut-transporters, taste receptors genes, sweet taste receptor T1R2T1R3, bitter taste receptors of the hTAS2gene family