Enteroendocrine localization of GLP-2 receptor expression in humans and rodents.
OBJECTIVE
Glucagon-like peptide (GLP)-2, a product of the proglucagon gene, is expressed in enteroendocrine cells of the small and large intestine and is trophic to the gastrointestinal mucosa. GLP-2 also inhibits gastric acid secretion and emptying and up-regulates intestinal hexose transport. GLP-2 acts via binding to a single G protein-coupled GLP-2 receptor (GLP-2R), but the cellular targets for the diverse actions of GLP-2 remain unknown.


METHODS
GLP-2R expression in rodent and human tissues was examined using a combination of Northern blotting, reverse-transcription polymerase chain reaction (RT-PCR), and immunocytochemistry.


RESULTS
A single major GLP-2R messenger RNA transcript was detected by Northern blot analysis in rodent stomach, duodenum, jejunum, ileum, and colon, but not in rodent esophagus. GLP-2R expression was also detected by RT-PCR in RNA from the hypothalamus, brain stem, and lung. Immunocytochemical localization of human GLP-2R expression using specific antisera detected GLP-2R immunopositivity in subsets of endocrine cell populations in the epithelium of the stomach and both the small and large bowel.


CONCLUSIONS
These findings suggest that enteroendocrine-derived GLP-2 acts directly on endocrine cells to induce one or more downstream mediators of GLP-2 action in the gastrointestinal tract.
Yusta
B
B
Department of Medicine, Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario, Canada.
Huang
L
L
Munroe
D
D
Wolff
G
G
Fantaske
R
R
Sharma
S
S
Demchyshyn
L
L
Asa
S L
SL
Drucker
D J
DJ
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001933:Brain Stem / Q000378:metabolism; D002478:Cells, Cultured; D004064:Digestive System / Q000378:metabolism; D004702:Endocrine Glands / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D008168:Lung / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D012333:RNA, Messenger; D018027:Receptors, Glucagon