Title :

A crosstalk between E2F1 and GLP-1 signaling pathways modulates insulin secretion

Author(s) :

Bourouh, Cyril [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Courty, Emilie [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Pasquetti, Gianni [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Gromada, Xavier [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Rabhi, Nabil [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Carney, Charlène [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Moreno, Maeva [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Boutry, Raphaël [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Rolland, Laure [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Caron, Emilie [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Benfodda, Zohra [Auteur]
Détection, évaluation, gestion des risques CHROniques et éMErgents (CHROME) / Université de Nîmes [CHROME]
Meffre, Patrick [Auteur]
Détection, évaluation, gestion des risques CHROniques et éMErgents (CHROME) / Université de Nîmes [CHROME]
Kerr-Conte, Julie [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Pattou, François [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Froguel, Philippe [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Hammersmith Hospital NHS Imperial College Healthcare
Bonnefond, Amélie [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Oger, Frédérik [Auteur]
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 [EGID]
Annicotte, Jean-Sébastien [Auteur correspondant]
Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]

Publication date :

2021-04-15

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Abstract Compromised β-cell function contributes to type 2 diabetes (T2D) development. The glucagon like peptide 1 (Glp-1) has emerged as a hormone with broad pharmacological potential toward T2D treatment, notably by ...
Show more >Abstract Compromised β-cell function contributes to type 2 diabetes (T2D) development. The glucagon like peptide 1 (Glp-1) has emerged as a hormone with broad pharmacological potential toward T2D treatment, notably by improving β-cell functions. Recent data have shown that the transcription factor E2f1, besides its role as a cell cycle regulator, is involved in glucose homeostasis by modulating β-cell mass, function and identity. Here, we demonstrate a crosstalk between the E2F1, phosphorylation of retinoblastoma protein (pRb) and Glp-1 signaling pathways. We found that β-cell specific E2f1 deficient mice ( E2f1 β−/− ) presented with impaired glucose homeostasis and decreased glucose stimulated-insulin secretion mediated by exendin 4 ( i . e ., GLP1R agonist), which were associated with decreased expression of Glp1r encoding Glp-1 receptor (GLP1R) in E2f1 β−/− pancreatic islets. Decreasing E2F1 transcriptional activity with an E2F inhibitor in islets from nondiabetic humans decreased GLP1R levels and blunted the incretin effect of exendin 4 on insulin secretion. Conversely, overexpressing E2f1 in pancreatic β cells increased Glp1r expression associated with enhanced insulin secretion mediated by GLP1R agonist. Interestingly, kinome analysis of mouse islets demonstrated that an acute treatment with exendin 4 increased pRb phosphorylation and subsequent E2f1 transcriptional activity. This study suggests a molecular crosstalk between the E2F1/pRb and GLP1R signaling pathways that modulates insulin secretion and glucose homeostasis.Show less >

Language :

Anglais

Collections :

• Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167

Source :

Harvested from HAL