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

Marine Grigoryan, Mamdouh H. Kedees, Maureen J. Charron, Yelena Guz, Gladys Teitelman

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)3076-3088
Number of pages13
JournalEndocrinology
Volume153
Issue number7
DOIs
StatePublished - Jul 2012

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Enteroendocrine Cells
Glucagon
Glucagon-Like Peptide 1
Cell Proliferation
Glucagon-Like Peptides
Peptides
Glucagon Receptors
Gastric Inhibitory Polypeptide
Cell Count
Intestinal Secretions
Hyperplasia
Cell Cycle
Transcription Factors
Stem Cells
Epithelial Cells
Hormones
Insulin
Glucose
Messenger RNA
Growth

ASJC Scopus subject areas

  • Endocrinology

Cite this

Regulation of mouse intestinal L cell progenitors proliferation by the glucagon family of peptides. / Grigoryan, Marine; Kedees, Mamdouh H.; Charron, Maureen J.; Guz, Yelena; Teitelman, Gladys.

In: Endocrinology, Vol. 153, No. 7, 07.2012, p. 3076-3088.

Research output: Contribution to journalArticle

Grigoryan, Marine ; Kedees, Mamdouh H. ; Charron, Maureen J. ; Guz, Yelena ; Teitelman, Gladys. / Regulation of mouse intestinal L cell progenitors proliferation by the glucagon family of peptides. In: Endocrinology. 2012 ; Vol. 153, No. 7. pp. 3076-3088.
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