Abstract
AbstractObjective. Dipeptidyl peptidase (DPP)-4 inhibitors inactivate glucagon-like peptide (GLP)-1, GLP-2, and other hormones by degradation. Administration of a DPP-4 inhibitor or GLP-2 analog stimulates intestinal growth and facilitates the restoration of mucosal damage caused by drug-induced colitis in mice. We studied the effect of GLP-2 deletion on morphological changes on gut and colitis recovery in mice deficient in proglucagon-derived peptides (PGDPs). Material and methods. Mice deficient in PGDPs were used. Eight-week-old male PGDPs−/− and PGDPs+/+ mice were sacrificed to examine the small intestine and colon morphology. To elucidate the effect of PGDP deletion on colitis, 12-week-old PGDPs−/− and PGDPs+/+ male mice were exposed to 2.5% dextran sulfate sodium (DSS) for 6 days. Colitis severity was assessed daily by disease activity index and body weight loss. Histological examinations were performed on days 7 and 21. Results. There were no differences in the height, width, and density of villous...
Highlights
The proglucagon gene is expressed in both pancreatic A and intestinal L cells (Eissele et al, 1994; Mojsov et al, 1986)
In the duodenum and three parts of the small intestine, deformities of the villous were not observed in the proglucagonderived peptides (PGDPs)−/− mice
Morphology Vasoactive intestinal peptide (VIP) knockout mice have marked deformities of the small intestine, which may be related to the fact that VIP is a downstream mediator of glucagon-like peptide (GLP)-2 (Yusta, Holland, Waschek, & Drucker, 2012)
Summary
The proglucagon gene is expressed in both pancreatic A and intestinal L cells (Eissele et al, 1994; Mojsov et al, 1986). The physiological actions of other intestinal PGDPs have been identified, in particular for GLP-2, which acts as a potent stimulator of growth in the small intestine of mice (Drucker, Erlich, Asa, & Brubaker, 1996). Rats treated by GLP-2 showed significantly increased small intestinal length, height of the villous and the depth of crypts, GLP-2 had no effect on the colon as measured by weight, length, and crypt depth (Kitchen et al, 2000). Inhibition of DPP-4 activity is, capable of prolonging the insulinotrophic effects of GLP-1 (Ahrén, 2007). DPP-4 inhibitor increases the intestinal weight, length, and morphometric data such as villous height and crypt depth of small intestine (Hartmann et al, 2000). Non-selective DPP-4 inhibitors (Yazbeck, Howarth, & Abbott, 2009), which bind to two other members of the DPP family, DPP-8 and DPP-9, ameliorate dextran sulfate sodium (DSS)-induced colitis in mice (Bank et al, 2006; Yazbeck et al, 2008, 2010)
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