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Cell Metab. 2015 Mar 3;21(3):379-91. doi: 10.1016/j.cmet.2015.02.005.

GLP-1R agonists promote normal and neoplastic intestinal growth through mechanisms requiring Fgf7.

Author information

1
Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G1X5, Canada.
2
Department of Physiology, University of Toronto, Toronto, ON M5S1A8, Canada.
3
Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G1X5, Canada. Electronic address: drucker@lunenfeld.ca.

Abstract

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.

PMID:
25738454
DOI:
10.1016/j.cmet.2015.02.005
[Indexed for MEDLINE]
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