Small intestine morphology and recovery after drug-induced colitis in proglucagon-derived peptides knockout mice

Abstract

Objective. 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 and the depth of crypt of small intestine, and the weight, length, and the crypt depth of colon between PGDPs−/− and PGDPs+/+. In DSS colitis, the decline and amelioration of disease activity index and body weight were not different between the PGDP−/− and PGDP+/+ mice. Histologically, the PGDP−/− mice showed significantly less recovery than showed by the PGDPs+/+ mice on day 21 (p < 0.05). Conclusion. Mice with PGDP deletion did not show morphological changes of gut. On colitis, PGDP deletion only caused less histological amelioration of colitis in the later phase of recovery.

Keywords

• small intestine morphology
• proglucagon-derived peptides
• drug-induced colitis
• glucagon-like peptide-2