Glucagon-like peptide-1 in the pathogenesis of obesity

The recently discovered gut peptide glucagon-like peptide-1 (GLP-1) is one of many peptides implicated in the short-term regulation of appetite. GLP-1 is a 30-amino-acid peptide that is produced in and secreted from the L cells of the intestinal mucosa after intake of a mixed meal. The amino acid sequence of GLP-1 is highly conserved and all mammals studied to date have identical GLP-1 sequences. GLP-1 receptors have been found in the lung and stomach, and binding of GLP-1 to skeletal muscle and fat cells has been demonstrated. At physiological plasma levels GLP-1 inhibits meal- and pentagastrin-induced gastric acid secretion. In addition, gastric emptying is delayed. Plasma GLP-1 is acutely elevated in normal-weight subjects after a meal, but obese subjects seem to have an attenuated GLP-1 release in response to meals. Consequently, GLP-1 may be a candidate for meal termination and intermeal satiety by either peripheral or central pathways. In terms of the importance of GLP-1 in the pathogenesis of obesity, research points in the direction of a vicious circle where overfeeding results in a down-regulation of postprandial GLP-1 release, which may result in the consumption of a larger amount of calories to elicit a "normal" GLP-1 satiety signal, thus perpetuating the obese state.