Glucagon-like peptide 1 as a regulator of food intake and body weight: therapeutic perspectives

After ingestion of carbohydrate- and fat-rich meals, the incretin hormone glucagon-like peptide 1 (GLP-1) is secreted from the L-cells in the distal put into the circulation. Its major physiological effect lies in a strongly glucose-dependent stimulation of insulin secretion from pancreatic B-cells. Furthermore, GLP-1 suppresses glucagon secretion, stimulates B-cell neogenesis as well as proinsulin biosynthesis and inhibits gastric emptying and acid secretion. Recently, GLP-1 could be shown to reduce caloric intake and to enhance satiety, most likely via specific receptors within the central nervous system, resulting in reduced weight gain in experimental animals. In nondiabetic and Type 2 diabetic human subjects, exogenous GLP-1 reduces hunger, caloric intake and body weight. Therefore, in addition to its well-characterized antidiabetogenic effect, the anorectic effect may offer GLP-1 a potential in the pharmacotherapy of obesity. It is still unknown whether the GLP-1 effect on caloric intake is sustained after long-term treatment. Furthermore, the exact mechanisms by which the peptide exerts its biological effects have not yet been clarified. Due to the rapid degradation of native GLP-1, its therapeutic application is limited by the short half-life. Therefore, suitable modes of administration are needed in order to reach stable plasma concentrations. The present review aims to describe the role of GLP-1 in the central regulation of feeding and to discuss its possible application in the pharmacotherapy of obesity. (C) 2002 Elsevier Science B.V. All rights reserved.