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
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.