mRNA levels of dipeptidyl peptidase IV decrease during intestinal adaptation.
BACKGROUND
Glucagon-like peptide 2 (GLP-2) has recently been shown to be a potent enterotrophic factor that may mediate mucosal hyperplasia during intestinal adaptation. The intestinal brush-border protease dipeptidyl peptidase IV (DPP IV) cleaves GLP-2 to an inactive form. It has been postulated that DPP IV activity limits the enterotrophic activity of GLP-2 in rats and humans. Massive small bowel resection (MSBR) in rats is an animal model of intestinal adaptation that has been used successfully to characterize factors involved in the modulation of adaptation.


METHODS
Total RNA was extracted from normal terminal ileum or terminal ileum post-MSBR from Sprague-Dawley rats which were sacrificed 2, 4, and 7 days postresection. A partial rat DPP IV clone was isolated by reverse transcription polymerase chain reaction, and Northern blot analysis of rat DPP IV mRNA levels in normal small bowel and small bowel post-MSBR was performed.


RESULTS
Within normal small bowel, DPP IV mRNA levels were greatest in the terminal ileum; levels in the duodenum and jejunum were approximately 50% of those in the terminal ileum. DPP IV mRNA levels decreased in terminal ileum post-MSBR 2, 4, and 7 days after resection.


CONCLUSIONS
The decreased DPPIV gene expression suggests a novel mechanism by which the effects on mucosal growth of GLP-2 may be further enhanced, and further that GLP-2 may be a more useful therapeutic agent in humans than currently anticipated.
Dunphy
J L
JL
Department of Medicine, Monash Medical Centre, Clayton, Victoria, 3168, Australia.
Justice
F A
FA
Taylor
R G
RG
Fuller
P J
PJ
D000222:Adaptation, Physiological; D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics*; D005934:Glucagon / Q000378:metabolism; D052216:Glucagon-Like Peptide 1; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D007422:Intestines / Q000201:enzymology / Q000502:physiology* / Q000601:surgery*; D010446:Peptide Fragments / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D053767:Glucagon-Like Peptide 2; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D012333:RNA, Messenger; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D018819:Dipeptidyl Peptidase 4