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

Overview

The aim is to further establish a physiological role for GLP-1 as an endogenous satiety signal by examining the effect of the specific GLP-1 receptor antagonist exendin (9-39) on appetite and food intake in healthy male subjects.

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.

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