Regulation of Mouse Intestinal L Cell Progenitors Proliferation by the Glucagon Family of Peptides
| Autor: | Maureen J. Charron, Marine Grigoryan, Mamdouh H. Kedees, Gladys Teitelman, Yelena Guz |
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| Rok vydání: | 2012 |
| Předmět: |
Male
endocrine system medicine.medical_specialty Enteroendocrine Cells Apoptosis Mice Transgenic Enteroendocrine cell Biology L Cells (Cell Line) Mice Paracrine signalling Endocrinology Internal medicine medicine Animals RNA Messenger Progenitor cell Crosses Genetic Cell Proliferation Mice Knockout Neurons Cell growth Cell Cycle digestive oral and skin physiology Diabetes-Insulin-Glucagon-Gastrointestinal Glucagon Intestines Gene Expression Regulation Glucagon-Like Peptides Goblet Cells Peptides Glucagon receptor hormones hormone substitutes and hormone antagonists Intestinal L Cells |
| Zdroj: | Endocrinology. 153:3076-3088 |
| ISSN: | 1945-7170 0013-7227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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