Glucagon-like peptide (GLP)-2 action in the murine central nervous system is enhanced by elimination of GLP-1 receptor signaling

Citation
J. Lovshin et al., Glucagon-like peptide (GLP)-2 action in the murine central nervous system is enhanced by elimination of GLP-1 receptor signaling, J BIOL CHEM, 276(24), 2001, pp. 21489-21499
Citations number
67
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
276
Issue
24
Year of publication
2001
Pages
21489 - 21499
Database
ISI
SICI code
0021-9258(20010615)276:24<21489:GP(AIT>2.0.ZU;2-T
Abstract
Glucagon-like peptide-2 (GLP-2) regulates energy homeostasis via effects on nutrient absorption and maintenance of gut mucosal epithelial integrity. T he biological actions of GLP-2 in the central nervous system (CNS) remain p oorly understood. We studied the sites of endogenous GLP-2 receptor (GLP-2R ) expression, the localization of transgenic LacZ expression under the cont rol of the mouse GLP-2R promoter, and the actions of GLP-2 in the murine CN S, GLP-2R expression was detected in multiple extrahypothalamic regions of the mouse and rat CNS, including cell groups in the cerebellum, medulla, am ygdala, hippocampus, dentate gyrus, pens, cerebral cortex, and pituitary, A 1.5-kilobase fragment of the mouse GLP-2R promoter directed LacZ expressio n to the gastrointestinal tract and CNS regions in the mouse that exhibited endogenous GLP-2R expression, including the cerebellum, amygdala, hippocam pus, and dentate gyrus, Intracerebroventricular injection of GLP-2 signific antly inhibited food intake during dark-phase feeding in wild-type mice. Di sruption of glucagonlike peptide-1 receptor (GLP-1R) signaling with the ant agonist exendin-(9-39) in wild-type mice or genetically in GLP-1R(-/-) mice significantly potentiated the anorectic actions of GLP-2, These findings i llustrate that CNS GLP-2R expression is not restricted to hypothalamic nucl ei and demonstrate that the anorectic effects of GLP-2 are transient and mo dulated by the presence or absence of GLP-1R signaling in vivo.