The essential role of insulin-like growth factor-1 in the intestinal tropic effects of glucagon-like peptide-2 in mice

Gastroenterology. 2006 Aug;131(2):589-605. doi: 10.1053/j.gastro.2006.05.055.


Background & aims: Glucagon-like peptide-2 (GLP-2) is an intestinal hormone that acts through unknown pathways to induce intestinal growth. We investigated the role of the insulin-like growth factors (IGF-1 and IGF-2) as mediators of GLP-2-enhanced growth in the murine intestine.

Methods: IGF-1 expression and secretion were determined in GLP-2-responsive primary intestinal cultures treated with GLP-2. Parameters of intestinal growth were assessed in wild-type (CD1, Igf1(+/+) and Igf2+), heterozygous (Igf1(+/-)), and null (Igf1(-/-) and Igf2(-P)) mice treated chronically with saline, GLP-2, IGF-1, or R-Spondin1.

Results: GLP-2 increased IGF-1 messenger RNA expression and IGF-1 secretion in intestinal cultures and increased expression of IGF-1 messenger RNA in mouse small intestine in vivo. Igf1(+/+) and Igf2+ mice responded to .1 microg/g(-1) per day(-1) GLP-2 with increased intestinal weights, morphometric parameters, and proliferative indices. In contrast, Igf1(-/-) mice were unresponsive to the same dose of GLP-2, failing to demonstrate changes in intestinal weight, morphometry, or proliferation. However, a significant effect of 1 microg/g(-1) per day(-1) GLP-2 was observed in Igf1(-/-) mice, but only in terms of small intestinal weight when normalized for body weight. Furthermore, Igf2(-P) mice demonstrated a partially impaired response in terms of small intestinal growth. Both Igf1(-/-) and Igf2(-P) mice exhibited normal-enhanced intestinal growth in response to IGF-1 and/or R-Spondin1.

Conclusions: GLP-2 enhances intestinal IGF-1 expression and secretion, and IGF-1 is required for small and large intestinal growth in response to GLP-2. These findings identify IGF-1 as an essential mediator of the intestinotropic actions of GLP-2.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptide-2 Receptor
  • Glucagon-Like Peptides / pharmacology*
  • Immunohistochemistry
  • In Vitro Techniques
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Intestine, Small / cytology
  • Intestine, Small / drug effects
  • Intestine, Small / growth & development*
  • Male
  • Mice
  • Mice, Knockout
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Receptors, Glucagon / genetics
  • Receptors, Glucagon / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction


  • Glucagon-Like Peptide 2
  • Glucagon-Like Peptide-2 Receptor
  • RNA, Messenger
  • Receptors, Glucagon
  • Glucagon-Like Peptides
  • Insulin-Like Growth Factor I
  • Glucagon-Like Peptide 1