Ontogeny of the glucagon-like peptide-2 receptor axis in the developing rat intestine.
Glucagon-like peptide-2 (GLP-2) is secreted by enteroendocrine cells in the small and large intestines and exerts intestinotropic effects in the gastrointestinal mucosal epithelium of the adult rodent. The actions of GLP-2 are mediated by the GLP-2 receptor, a new member of the G protein-coupled receptor superfamily. To ascertain whether the GLP-2/GLP-2 receptor axis is expressed and functional in the developing intestine, we have studied the synthesis of GLP-2 and the expression of the GLP-2 receptor (GLP-2R) in the fetal and neonatal rat gut. GLP-2 immunoreactivity (GLP-2-IR) was detected in the fetal rat intestine, and fetal rat intestinal cell cultures secreted correctly processed GLP-2(1-33) into the medium. High levels of GLP-2(1-33) were also detected in the circulation of 13-day-old neonatal rats (P < 0.001 vs. adult). Analysis of GLP-2 receptor expression by RT-PCR demonstrated GLP-2R messenger RNA transcripts in fetal intestine and in neonatal stomach, jejunum, ileum, and colon. The levels of GLP-2R messenger RNA transcripts were comparatively higher in the fetal and neonatal intestine (P < 0.05-001 vs. adult) and declined to adult levels by postnatal day 21. Subcutaneous administration of a degradation-resistant GLP-2 analog, h[Gly2]-GLP-2 once daily for 10 days increased stomach (0.009 +/- 0.0003 vs. 0.007 +/- 0.002 g/g body mass, h[Gly2]-GLP-2-treated vs. controls; P < 0.05) and small bowel weight (0.043 +/- 0.0037 vs. 0.031 +/- 0.0030 g/g body mass; P < 0.05). h[Gly2]-GLP-2 also increased both small (2.4 +/- 0.05 vs. 1.8 +/- 0.17 cm/g body mass; P < 0.05) and large bowel length (0.32 +/- 0.01 vs. 0.25 +/- 0.02 cm/g body mass, h[Gly2]-GLP-2-treated vs. saline-treated controls, respectively; P < 0.05) in neonatal rats. These findings demonstrate that both components of the GLP-2/GLP-2 receptor axis are expressed in the fetal and neonatal intestine. The ontogenic regulation and functional integrity of this axis raises the possibility that GLP-2 may play a role in the development and/or maturation of the developing rat intestine.
Lovshin
J
J
Department of Physiology, Toronto General Hospital, Banting and Best Diabetes Center, University of Toronto, Ontario, Canada.
Yusta
B
B
Iliopoulos
I
I
Migirdicyan
A
A
Dableh
L
L
Brubaker
P L
PL
Drucker
D J
DJ
D000818:Animals; D000831:Animals, Newborn; D003106:Colon / Q000187:drug effects / Q000254:growth & development; D015870:Gene Expression; D005934:Glucagon / Q000235:genetics; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D007413:Intestinal Mucosa / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000254:growth & development; D007422:Intestines / Q000196:embryology / Q000254:growth & development*; D009929:Organ Size / Q000187:drug effects; D010455:Peptides / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000187:drug effects / Q000254:growth & development
C000593835:Glp1r protein, rat; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D018027:Receptors, Glucagon; D052336:Proglucagon; D004763:Glucagon-Like Peptides; D005934:Glucagon