Glucagon-Like Peptide 2 Is an Endogenous Mediator of Postresection Intestinal Adaptation

Abstract

Background: After massive small bowel resection, the remnant intestine undergoes compensatory adaptation. We tested the hypothesis that glucagon-like peptide-2 (GLP-2) is an endogenous mediator of postresection intestinal adaptation. Methods: Rats were allocated to 1 of 4 groups: groups 1 and 2 rats underwent mid-small bowel transection and reanastomosis; groups 3 and 4 rats underwent 75% mid-small bowel resection and reanastomosis. Groups 2 and 4 rats were administered 1.8 mg of antirat GLP-2 antibody twice daily beginning immediately after the surgical procedure; groups 1 and 3 rats were administered rabbit serum (control). Ileal specimens were harvested on postoperative day 7. Results: Ileal mucosa from group 3 animals displayed morphologic and proliferative indices of adaptation. Each of these indices of adaptation was inhibited by GLP-2 immunoneutralization (group 4). Morphologic and proliferative parameters in the ileum from animals that had undergone transection with reanastomosis were unaffected by GLP-2 immunoneutralization. Conclusions: These results suggest that GLP-2 is an endogenous mediator of postresection intestinal adaptation.

Intraperitoneal administration of a blocking antibody to glucagon-like peptide 2 (GLP-2) significantly blunted mucosal hypertrophy and epithelial proliferation in the rat ileum after intestinal resection. This study suggests that GLP-2 is in part responsible for the adaptive response typically found after massive small bowel resection.

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