The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion
- Conditions
- To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion
- Interventions
- Registration Number
- NCT01656057
- Lead Sponsor
- Filip Krag Knop
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 10
- HbA1c < 6,0%
- Not anaemic
- Written informed consent
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Acetaminophen+saline Saline Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline Colesevelam+saline Saline Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline Colesevelam+CCK Acetaminophen Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour Acetaminophen+CCK Acetaminophen Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour Acetaminophen+CCK Cholecystokinin-8 Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour Metformin+saline Saline Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline Metformin+CCK Cholecystokinin-8 Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour Colesevelam+saline Colesevelam Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline Colesevelam+CCK Cholecystokinin-8 Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour Acetaminophen+saline Acetaminophen Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline Metformin+saline Acetaminophen Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline Metformin+saline Metformin Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + i.v. saline Metformin+CCK Acetaminophen Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour Metformin+CCK Metformin Metformin tablet 1500 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour Colesevelam+saline Acetaminophen Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. saline Colesevelam+CCK Colesevelam Colesevelam tablet 3750 mg + Acetaminophen tablet 1500 mg via nasogastric tube + iv. CCK-8, 24 pmol/kg/hour
- Primary Outcome Measures
Name Time Method GLP-1 response as incremental area under curve (iAUC) -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
- Secondary Outcome Measures
Name Time Method Insulin -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Trial Locations
- Locations (1)
University Hospital of Copenhagen, Gentofte Hospital, Diabetic Research Division
🇩🇰Copenhagen, Hellerup, Denmark