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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
10
Acetaminophen dissolved in 50 ml of water
Metformin + acetaminophen dissolved in 50 ml of water
Colesevelam + acetaminophen dissolved in 50 ml of water
iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes
iv. saline infusion 40 ml/hour for the first 60 minutes
University Hospital of Copenhagen, Gentofte Hospital, Diabetic Research Division
Copenhagen, Hellerup, Denmark
GLP-1 response as incremental area under curve (iAUC)
Time frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
Insulin
Time frame: -30, -15, 0, 10, 20, 30, 40, 50, 60, 90, 120, 150, 180, 240
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