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 TV (DPP IV) cleaves GLP-2 to an inactive form. It has been postulated that DPP TV 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 TV clone was isolated by reverse transcription polymerase chain reaction, and Northern blot analysis of rat DPP TV 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 similar to 50% of those in the terminal ileum. DPP TV mRNA levels decreased in terminal ileum post-MSBR 2, 4, and 7 days after resection. Conclusion. 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. (C) 1999 Academic Press.