The Impact of Gall Bladder Emptying and Bile Acids on the Human GLP-1-secretion

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.

Conditions

• To Assess the Impact of Bile Acids on Human Glukagon-like-peptide-1 Secretion

Interventions

DRUG

Acetaminophen

Acetaminophen dissolved in 50 ml of water

DRUG

Metformin

Metformin + acetaminophen dissolved in 50 ml of water

DRUG

Colesevelam

Colesevelam + acetaminophen dissolved in 50 ml of water

OTHER

Cholecystokinin-8

iv. infusion of CCK-8, 24 pmol/kg/hour for the first 60 minutes

OTHER

Saline

iv. saline infusion 40 ml/hour for the first 60 minutes

Sponsors & Collaborators

• University of Copenhagen

  collaborator OTHER

• Filip Krag Knop

  lead OTHER

Principal Investigators

• Ulrich Rohde, MD · Diabetic Research Division, Department of Internal Medicine, University Hospital of Copenhagen, Gentofte Hospital

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

40 Years

Sex

MALE

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2012-07-31

Primary Completion

2013-10-31

Completion

2014-04-30

Countries

• Denmark