Echolocation
Conditions
Keywords
GI-physiology, CDCA, bile acids, TGR5, satiation peptides
Brief summary
The purpose of this study is do determine the functional significance of the G protein-coupled receptor TGR5 in the secretion of GI satiation peptides by using natural bile acids and oleanolic acid (triterpenoid compound of plant origin) as TGR5 agonists.
Detailed description
TGR5 is expressed in GLP-1-secreting cell lines and L cells from mice; gain- and loss-of-function models suggest a physiological role for TGR5 activation on GLP-1 secretion in rodents. TGR5 signaling showed improved postprandial glucose tolerance in obese mice, associated with marked postprandial GLP-1 release and insulin secretion. In contrast, TGR5-/- mice exhibited reduced glucose tolerance. In animals, TGR5 activation has been shown for natural bile acids (BAs) and triterpenoid compounds of plant origin, such as oleanolic acid (OA), suggesting a role for postprandial BAs in modulating nutrient-induced GLP-1 secretion. We therefore hypothesized that intraduodenal (ID) perfusions of TGR5 agonists (BAs and OA) stimulate the secretion of GLP-1 with respective changes in the glucose metabolism of healthy humans.
Interventions
OTHERsaline
intraduodenal perfusion
OTHERbile acid (CDCA, chenodeoxycholic acid)
intraduodenal perfusion
OTHERoleanolic acid
intraduodenal perfusion
DIETARY_SUPPLEMENToleic acid
intraduodenal perfusion
Sponsors
University Hospital, Basel, Switzerland
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy subjects * BMI of 19.0-24.5 * Age 18-40 * Stable body weight for at least 3 months
Exclusion criteria
* Smoking * Substance abuse * Regular intake of medication * Medical of psychiatric illness * Gastrointestinal disorders or food allergies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal satiation peptide secretion | 3 hours blood sampling | Assessment of plasma GLP-1, PYY and CCK release to BA and OA stimulation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum bile acids | 3 hours blood sampling | Assessment of serum bile acids levels to BA and OA stimulation |
| Appetite perceptions during 3 hours using visual analogue scales | 3 hours | Assessment of the following appetite perceptions markers: feelings of hunger, feelings of prospective food consumption, feelings of fullness and feelings of satiety using validated visual analogue scales |
| Glucose and insulin secretion | 3 hours blood sampling | Assessment of plasma glucose and insulin levels to BA and OA stimulation |
Countries
Switzerland
Outcome results
None listed