The Role of Glucagon-Like Peptide-1 (Glp-1) in Eating Behavior

Abstract

Glucagon-like peptide-1 (GLP-1) is a posttranslational product of proglucagon gene expression. It is released from the α-cells of the pancreas, L-cells of the small intestine and colon, and neurons in the central nervous system. Secretion of GLP-1 is governed by neural-humoral reflex, the presence of nutrients, and other endocrine factors in the intestinal tract. GLP-1 is present in two forms, GLP-1_1–36 and GLP-1_1–37, which undergo enzymatic cleavage to yield the bioactive forms of the peptide: GLP-1_7–36 and GLP-1_7–37, which enter the circulation via the lymphatic system. Most of the peptide is rapidly degraded by dipeptidyl peptidase IV (DPP-IV), which results in a relatively short half-life in the circulation. GLP-1 has potent effects on (1) regulating gastrointestinal functions such as gastric emptying, motility, and pancreatic secretions; (2) suppression of food intake; and (3) regulation of blood glucose levels by stimulating insulin secretion. Both systemic as well as central GLP-1 is effective in decreasing food intake either by acting locally or through vagal afferents and brain neurons that maintain synaptic connections with GLP-1-producing neurons. GLP-1 interacts with both central and peripheral peptides that control food intake as well as with long-term energy-regulating hormones. In pathological states characterized by imbalanced energy homeostasis, GLP-1 secretion is markedly decreased, but potency is largely maintained. This chapter summarizes the role of GLP-1 as a molecule signal reducing food intake, its mechanisms of action, and its potential participation in the regulation of energy homeostasis and metabolical abnormalities.