Exogenous GLP-2 and IGF-I induce a differential intestinal response in IGF binding protein-3 and -5 double knockout mice.

Abstract

Glucagon-like peptide-2 (GLP-2) action is dependent on intestinal expression of IGF-I, and IGF-I action is modulated by IGF binding proteins (IGFBP). Our objective was to evaluate whether the intestinal response to GLP-2 or IGF-I is dependent on expression of IGFBP-3 and -5. Male, adult mice in six treatment groups, three wild-type (WT) and three 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 7 days. 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.

• Authors: Sangita G Murali, Adam S Brinkman, Patrick Solverson, Wing Pun, John E Pintar, Denise M Ney
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 302 Issue 8 Pg. G794-804 (Apr 15 2012) ISSN: 1522-1547 [Electronic] United States
• PMID: 22281475 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Glucagon-Like Peptide 2
• Insulin-Like Growth Factor Binding Protein 3
• Insulin-Like Growth Factor Binding Protein 5
• RNA
• Insulin-Like Growth Factor I

Topics

• Analysis of Variance
• Animals
• Body Weight (genetics, physiology)
• Colon (anatomy & histology, drug effects, growth & development)
• Genes, erbB (physiology)
• Glucagon-Like Peptide 2 (pharmacology)
• Insulin-Like Growth Factor Binding Protein 3 (genetics, physiology)
• Insulin-Like Growth Factor Binding Protein 5 (genetics, physiology)
• Insulin-Like Growth Factor I (pharmacology)
• Intestinal Mucosa (drug effects, growth & development)
• Intestine, Small (anatomy & histology, drug effects, growth & development)
• Intestines (anatomy & histology, drug effects, growth & development)
• Kidney (growth & development)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Organ Size (genetics, physiology)
• RNA (biosynthesis, isolation & purification)
• Real-Time Polymerase Chain Reaction
• Spleen (growth & development)