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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / metabolism
  • Cell Proliferation / physiology
  • Colon / metabolism*
  • Colon / physiology
  • Colon / physiopathology
  • Epidermal Growth Factor / metabolism
  • Exenatide
  • Female
  • Fibroblast Growth Factor 7 / metabolism*
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Glucagon-Like Peptide-1 Receptor / metabolism*
  • Incretins / metabolism
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / physiology
  • Intestinal Mucosa / physiopathology
  • Intestine, Small / metabolism*
  • Intestine, Small / pathology
  • Intestine, Small / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Peptides / metabolism
  • Receptor, IGF Type 1 / metabolism
  • Signal Transduction / physiology
  • Venoms / metabolism


  • Fgf7 protein, mouse
  • Glucagon-Like Peptide-1 Receptor
  • Incretins
  • Peptides
  • Venoms
  • Fibroblast Growth Factor 7
  • Epidermal Growth Factor
  • Exenatide
  • Receptor, IGF Type 1

Associated data

  • GEO/GSE63841