Glucagon-like peptide-1 (7-36) amide: a central regulator of satiety and interoceptive stress

Glucagon-like peptide-1 (7-36) amide (GLP-1) is processed from proglucagon in the distal ileum as well as in the CNS. In the periphery, GLP-1 acts as an incretin factor and profoundly inhibits upper gastrointestinal motility ('ileal brake'), the latter presumably involving the CNS. Within the CNS, GLP-1 has a satiating effect, since administration of GLP-1 into the third cerebral ventricle reduces short-term food intake (and meal size), while administration of GLP-1 antagonists have the opposite effect. In addition, activation of GLP-1 receptors in certain brain regions elicits strong taste aversions. Similarities between toxin- and GLP-1-induced neuronal activity in the CNS (brain stem) suggest a role for central GLP-1 receptors in relaying interoceptive stress. Thus, regionally distinct GLP-1 receptor populations in the CNS may be involved in satiety or malaise. It is argued that the satiating and aversive aspects of GLP-1 serve homeostatic and nonhomeostatic functions with respect to maintenance of nutrient balance.