| First Author | Koehler JA | Year | 2015 |
| Journal | Cell Metab | Volume | 21 |
| Issue | 3 | Pages | 379-91 |
| PubMed ID | 25738454 | Mgi Jnum | J:220706 |
| Mgi Id | MGI:5635961 | Doi | 10.1016/j.cmet.2015.02.005 |
| Citation | Koehler JA, et al. (2015) GLP-1R agonists promote normal and neoplastic intestinal growth through mechanisms requiring Fgf7. Cell Metab 21(3):379-91 |
| abstractText | Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L cells promotes nutrient disposal via the incretin effect. However, the majority of L cells are localized to the distal gut, suggesting additional biological roles for GLP-1. Here, we demonstrate that GLP-1 receptor (GLP-1R) signaling controls mucosal expansion of the small bowel (SB) and colon. These actions did not require the epidermal growth factor (EGF) or intestinal epithelial insulin-like growth factor (IGF1) receptors but were absent in Glp1r(-/-) mice. Polyp number and size were increased in SB of exendin-4-treated Apc(Min/+) mice, whereas polyp number was reduced in SB and colon of Glp1r(-/-):Apc(Min/+) mice. Exendin-4 increased fibroblast growth factor 7 (Fgf7) expression in colonic polyps of Apc(Min/+) mice and failed to increase intestinal growth in mice lacking Fgf7. Exogenous exendin-4 and Fgf7 regulated an overlapping set of genes important for intestinal growth. Thus, gain and loss of GLP-1R signaling regulates gut growth and intestinal tumorigenesis. |
