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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)

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