Document Detail

Regulation of mouse intestinal L cell progenitors proliferation by the glucagon family of peptides.
MedLine Citation:
PMID:  22569789     Owner:  NLM     Status:  MEDLINE    
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.
Marine Grigoryan; Mamdouh H Kedees; Maureen J Charron; Yelena Guz; Gladys Teitelman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-08
Journal Detail:
Title:  Endocrinology     Volume:  153     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-25     Completed Date:  2012-09-20     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3076-88     Citation Subset:  AIM; IM    
Department of Cell Biology, State University of New York-Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, USA.
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MeSH Terms
Cell Cycle
Cell Proliferation
Crosses, Genetic
Enteroendocrine Cells / cytology*,  metabolism
Gene Expression Regulation*
Glucagon / metabolism*
Goblet Cells / cytology
Intestines / cytology*
Mice, Knockout
Mice, Transgenic
Neurons / metabolism
Peptides / chemistry
RNA, Messenger / metabolism
Grant Support
Reg. No./Substance:
0/Peptides; 0/RNA, Messenger; 9007-92-5/Glucagon

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