Comparative Effects of Glucagon‐Like Peptide‐2 (GLP‐2), Growth Hormone (GH), and Keratinocyte Growth Factor (KGF) on Markers of Gut Adaptation After Massive Small Bowel Resection in Rats

Abstract

GLP-2 exerts superior trophic effects on jejunal growth and also improves mucosal glutathione redox status throughout the bowel after massive SBR in rats. Both GH and KGF increase colonic mucosal growth in this model. KGF alone potently increases gut mucosal goblet cell number and expression of the cytoprotective trefoil peptide TFF3. The differential effects of GLP-2, GH and KGF administration in this model of short bowel syndrome suggest that individual therapy with these growth factors may not be an adequate strategy to maximally improve adaptive gut mucosal growth and cytoprotection after massive small intestinal resection. Future research should address the use of these agents in combination in short bowel syndrome.

Chronically administered retinoic acid has trophic effects in the rat small intestine and promotes adaptation in a resection model of short bowel syndrome

“…Quantification of lipid peroxidation and ␣-tocopherol along the crypt-villus axis are consistent with increased oxidative stress in crypt stem cells and villus tip cells (29). Furthermore, following partial small bowel resection, the glutathione redox potential is shifted to a more oxidized state in the ileal remnant (62). Thus the observed prosurvival effects of RA postresection may be mediated by reducing oxidant stress in actively proliferating crypt cells.…”

The influence of nutrients, biliary-pancreatic secretions, and systemic trophic hormones on intestinal adaptation in a Roux-en-Y bypass model

“…5). It was something of a surprise that neither of these factors appeared to be linked to the decreases in apoptosis seen in the bypass animals because they both have been suggested to play a role in the control of mucosal apoptosis [46,47]. Thus, it may be other factors, specific signals, a combination of factors, or variations in the sensitivity to trophic ligands induced by changes in receptor expression, which control apoptosis and the morphological adaptation that is stimulated by nutrient contact [46,48].…”

Frontiers in glucagon-like peptide-2: multiple actions, multiple mediators

“…This is in contrast to the more marked effect of IGF-I ablation on both small and large intestinal growth responses to GLP-2. Moreover, unlike IGF-I, KGF treatment produces differential effects to those of GLP-2, affecting mainly colonic growth and the differentiation of goblet cells (2,22,42). Indeed, Ørskov et al (32) found that the GLP-2-induced increase in mucin expression was blocked by KGF antibodies, suggesting that the specific role of KGF may be to promote colonic goblet cell differentiation in response to GLP-2.…”