| First Author | Bourouh C | Year | 2022 |
| Journal | Cell Rep | Volume | 40 |
| Issue | 6 | Pages | 111170 |
| PubMed ID | 35947949 | Mgi Jnum | J:328277 |
| Mgi Id | MGI:7334665 | Doi | 10.1016/j.celrep.2022.111170 |
| Citation | Bourouh C, et al. (2022) The transcription factor E2F1 controls the GLP-1 receptor pathway in pancreatic beta cells. Cell Rep 40(6):111170 |
| abstractText | 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 beta cell functions. The cell-cycle regulator and transcription factor E2f1 is involved in glucose homeostasis by modulating beta cell mass and function. Here, we report that beta cell-specific genetic ablation of E2f1 (E2f1(beta-/-)) impairs glucose homeostasis associated with decreased expression of the Glp-1 receptor (Glp1r) in E2f1(beta-/-) 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 beta 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 beta cell function and suggest molecular crosstalk between the E2F1/pRb and GLP1R signaling pathways. |
