To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion
Conditions
Keywords
Bile acids, Gall bladder emptying, Human, Glucagon like peptide 1, GLP-1
Brief summary
The last couple of years it has been shown that bile acids not only acts as simple emulsifiers of fat, but constitutes a complex metabolic integrator which not only have an influence on fat digestion and lipid metabolism, but also modulates the energy expenditure in (brown) adipose tissue and muscle tissue. This action is due to stimulation of the receptor TGR5 by bile acids. Recently scientists have discovered that this receptor in rodents is also expressed on the surface of intestinal L-cells (which normally secrets Glucagon-Like Peptide-1 (GLP-1) in response to nutrient stimulation). The stimulation of this receptor has shown a GLP-1 secretion from the intestinal cells which is interesting since GLP-1 has a central role in maintaining normal glucose tolerance and thus blood sugar. Given the above, bile acids has an important impact on intestinal GLP-1 secretion. Whether these scientific findings can be proven in human beings is uncertain. The primary hypothesis is that stimulating gall bladder emptying via Cholecystokinin (CCK) in healthy subjects will result in a significant GLP-1 response. We also hypothesize that adding orally Metformin or a sequestrant (a bile acid binder) will further enhance this GLP-1 response.
Interventions
DRUGAcetaminophen
Acetaminophen dissolved in 50 ml of water
DRUGMetformin
Metformin + acetaminophen dissolved in 50 ml of water
DRUGColesevelam
Colesevelam + acetaminophen dissolved in 50 ml of water
OTHERCholecystokinin-8
iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes
OTHERSaline
iv. saline infusion 40 ml/hour for the first 60 minutes
Sponsors
University of Copenhagen
Filip Krag Knop
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* HbA1c \< 6,0% * Not anaemic * Written informed consent
Exclusion criteria
* Liver disease * Nephropathy * fasting plasma glucose \> 5,6mM * Diabetes running in the family (parents or grandparents) * Any medical treatment * A former medical history of liver- or bile disease * any surgical procedure conducted in the abdomen * Body mass index \< 18,5 kg/m2 or \> 25 kg/m2
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| GLP-1 response as incremental area under curve (iAUC) | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
Secondary
| Measure | Time frame |
|---|---|
| Insulin | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
Other
| Measure | Time frame |
|---|---|
| Glucagon-Like Peptide-2 | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
| Peptide YY | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
| Oxyntomodulin | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
| Glucose-Dependent Insulinotropic Peptide | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
| Bile acids | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
| c-peptide | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
| CCK | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
| Gall bladder emptying assessed ultrasonically | -30, -15, 20, 40, 60, 90, 120, 150, 180 |
| Resting energy expenditure | -10, 50, 210 |
| Estimation of satiety via visual analogue scale | 0, 30, 60, 90, 120, 150, 180, 240 |
| Gastrin | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
| glucagon | -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240 |
Countries
Denmark
Outcome results
None listed