Insulin-like growth factor-1 (IGF-1), a known secretory product of intestinal subepithelial myofibroblasts (ISEMF), is essential for the intestinotrophic effects of glucagon-like peptide-2(GLP-2). I hypothesized that GLP-2 increases the production of IGF-1 by primary murine
ISEMF in culture. Immunocytochemistry showed that the ISEMF stained appropriately for α
smooth muscle actin and vimentin but not for desmin. The ISEMF also expressed GLP-2
receptor and IGF-1 mRNA transcripts. ISEMF treated with GLP-2 revealed a maximal increase in IGF-1 mRNA transcript levels at 10-8 M GLP-2 and 2hr. Interestingly, immunoblotting revealed an increase in P-AKT/T-AKT with GLP-2, but no changes in cAMP, P-ERK/T-ERK or calcium were detected. PI3K inhibition and kinase-dead AKT over-expression abrogated GLP-2-induction of IGF-1 mRNA, and ISEMF from GLP-2R null mice demonstrated reductions in IGF-1 mRNA and cellular IGF-1, but not in media IGF-1, vs. wild-type ISEMF. These findings suggest a possible mechanism by which GLP-2 increases intestinal growth in-vivo.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/18828 |
| Date | 15 February 2010 |
| Creators | Leen, Jason |
| Contributors | Brubaker, Patricia |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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