title: 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.
authors.affiliation: Department of Cell Biology, State University of New York-Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York 11203, USA.
authors.forename: Marine
authors.initials: M
authors.lastname: Grigoryan
authors.forename: Mamdouh H
authors.initials: MH
authors.lastname: Kedees
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Charron
authors.forename: Yelena
authors.initials: Y
authors.lastname: Guz
authors.forename: Gladys
authors.initials: G
authors.lastname: Teitelman
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D049109:Cell Proliferation; D003433:Crosses, Genetic; D019858:Enteroendocrine Cells / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D005934:Glucagon / Q000378:metabolism*; D020397:Goblet Cells / Q000166:cytology; D007422:Intestines / Q000166:cytology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D010455:Peptides; D012333:RNA, Messenger; D005934:Glucagon