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Article Dans Une Revue Cell Reports Année : 2022

The transcription factor E2F1 controls the GLP-1 receptor pathway in pancreatic β cells

Résumé

The glucagon-like peptide 1 (Glp-1) has emerged as a hormone with broad pharmacological potential in type 2 diabetes (T2D) treatment, notably by improving β cell functions. The cell-cycle regulator and transcription factor E2f1 is involved in glucose homeostasis by modulating β cell mass and function. Here, we report that β cell-specific genetic ablation of E2f1 (E2f1β−/−) impairs glucose homeostasis associated with decreased expression of the Glp-1 receptor (Glp1r) in E2f1β−/− pancreatic islets. Pharmacological inhibition of E2F1 transcriptional activity in nondiabetic human islets decreases GLP1R levels and blunts the incretin effect of GLP1R agonist exendin-4 (ex-4) on insulin secretion. Overexpressing E2f1 in pancreatic β cells increases Glp1r expression associated with enhanced insulin secretion mediated by ex-4. Interestingly, ex-4 induces retinoblastoma protein (pRb) phosphorylation and E2f1 transcriptional activity. Our findings reveal critical roles for E2f1 in β cell function and suggest molecular crosstalk between the E2F1/pRb and GLP1R signaling pathways.
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Dates et versions

hal-03810743 , version 1 (01-06-2023)

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Cyril Bourouh, Emilie Courty, Laure Rolland, Gianni Pasquetti, Xavier Gromada, et al.. The transcription factor E2F1 controls the GLP-1 receptor pathway in pancreatic β cells. Cell Reports, 2022, 40 (6), pp.111170. ⟨10.1016/j.celrep.2022.111170⟩. ⟨hal-03810743⟩
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