Glucagon-like peptide-2 (GLP-2) action is dependent on intestinal expression of insulin-like growth factor-I (IGF-I) and IGF-I action is modulated by IGF binding proteins (IGFBP). Our objective was to evaluate if the intestinal response to GLP-2 or IGF-I is dependent on expression of IGFBP-3 and -5. Male, adult mice in 6 treatment groups, 3 wild type (WT) and 3 double IGFBP-3/-5 knockout (KO), received twice daily intraperitoneal injections of GLP-2 (0.5 µg/g body wt), IGF-I (4 µg/g body wt) or PBS (vehicle) for 7d. IGFBP-3/-5 KO mice showed a phenotype of lower plasma IGF-I concentration, but greater body weight and relative mass of visceral organs, compared with WT mice, p<0.001. WT mice showed jejunal growth with either IGF-I or GLP-2 treatment. In KO mice, IGF-I did not stimulate jejunal growth, crypt mitosis, sucrase activity and IGF-I receptor (IGF-IR) expression suggesting that the intestinotrophic actions of IGF-I are dependent on expression of IGFBP-3 and -5. In KO mice, GLP-2 induced significant increases in jejunal mucosal cellularity, crypt mitosis, villus height and crypt depth that was associated with increased expression of the ErbB ligand epiregulin and decreased expression of IGF-I and IGF-IR. This suggests that in KO mice, GLP-2 action in jejunal mucosa is independent of the IGF-I system and linked with ErbB ligands. In summary, the intestinotrophic actions of IGF-I, but not GLP-2, in mucosa are dependent on IGFBP-3 and -5. These findings support the role of multiple downstream mediators for the mucosal growth induced by GLP-2.
- intestinal adaptation
- Copyright © 2011, American Journal of Physiology- Gastrointestinal and Liver Physiology