Intestinal Glucagon-like Peptide-1 (GLP-1) and the Physiological Role in Eating in Humans

Understanding the exact mechanisms by which GLP-1 inhibits eating can be crucial in order to convert its anorectic action into useful, safe and effective drugs. So far, it is however not clear to what extent GLP-1 is a hormonal regulator of eating or whether the observed effects are rather a pharmacological phenomenon. By applying classical algorithms from endocrinology several criteria must be fulfilled before a hormone can be considered an endogenous physiological satiety signal. One is that exogenous administration of a selective antagonist should prevent the eating-inhibitory effect of GLP-1. At present, cholecystokinin (CCK) is the only peptide in humans identified to fit these criteria. For intestinal GLP-1, it has not been investigated whether a specific GLP-1 receptor antagonist can block the eating-inhibitory effect in humans. The availability of a specific GLP-1 receptor antagonist, exendin (9-39), now makes it possible to further investigate this pathway. Exendin (9-39), is a powerful tool available for human use to characterize of endogenous GLP-1 as a physiological regulator of different biological functions. The molecule has been used to document that endogenous GLP-1 is an important incretin hormone and a regulator of antro-pyloro-duodenal motility. The role of endogenous GLP-1 in regulating food intake and appetite has, however, not been investigated before.

Inclusion criteria

• Healthy male subject with a BMI of 19-25 m2/kg
• Stable body weight for at least three months
• Normal eating habits
• Age between 18 and 45 years
• Sufficient understanding of the German language
• Subjects understand the procedures and the risks associated with the study
• Participants must be willing to adhere to the protocol and sign the consent form

Exclusion criteria

• Participation in another clinical trial (currently or within the last 30 days)
• Smoking
• Substance abuse
• Regular intake of medications (except for oral contraceptives)
• Chronic or acute medical condition including clinically relevant abnormality in physical exam or laboratory values
• History of gastrointestinal disorders
• Food allergies