HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Regulation of mouse intestinal L cell progenitors proliferation by the glucagon family of peptides.

Abstract
Glucagon like peptide-1 (GLP-1) and GLP-2 are hormones secreted by intestinal L cells that stimulate glucose-dependent insulin secretion and regulate intestinal growth, respectively. Mice with deletion of the glucagon receptor (Gcgr) have high levels of circulating GLP-1 and GLP-2. We sought to determine whether the increased level of the glucagon-like peptides is due to L cell hyperplasia. We found, first, that high levels of the glucagon-like peptides increase L cell number but does not affect the number of other intestinal epithelial cell types. Second, a large proportion of ileal L cells of Gcgr(-/-) mice coexpressed glucose-dependent insulinotropic peptide (GIP). Cells coexpressing GIP and GLP-1 are termed LK cells. Third, the augmentation in L cell number was due to a higher rate of proliferation of L cell progenitors rather than to the entrance of mature L cells into the cell cycle. Fourth, a high concentration of the glucagon-like peptides in the circulation augmented the mRNA levels of transcription factors expressed by late but not early enteroendocrine progenitors. Fifth, the administration of exendin 9-39, a GLP-1 receptor antagonist, resulted in a decrease in the rate of L cell precursor proliferation. Finally, we determined that L cells do not express the GLP-1 receptor, suggesting that the effect of GLP-1 is mediated by paracrine and/or neuronal signals. Our results suggest that GLP-1 plays an important role in the regulation of L cell number.
AuthorsMarine Grigoryan, Mamdouh H Kedees, Maureen J Charron, Yelena Guz, Gladys Teitelman
JournalEndocrinology (Endocrinology) Vol. 153 Issue 7 Pg. 3076-88 (Jul 2012) ISSN: 1945-7170 [Electronic] United States
PMID22569789 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Peptides
  • RNA, Messenger
  • Glucagon
Topics
  • Animals
  • Apoptosis
  • Cell Cycle
  • Cell Proliferation
  • Crosses, Genetic
  • Enteroendocrine Cells (cytology, metabolism)
  • Gene Expression Regulation
  • Glucagon (metabolism)
  • Goblet Cells (cytology)
  • Intestines (cytology)
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Neurons (metabolism)
  • Peptides (chemistry)
  • RNA, Messenger (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: