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

被引：9

作者：

Bourouh, Cyril ^{[1
]}

Courty, Emilie ^{[1
,2
]}

Rolland, Laure ^{[1
,2
]}

Pasquetti, Gianni

Gromada, Xavier ^{[1
]}

Rabhi, Nabil ^{[3
,4
]}

Carney, Charlene ^{[1
]}

Moreno, Maeva ^{[1
]}

Boutry, Raphael ^{[1
]}

Caron, Emilie ^{[5
]}

Benfodda, Zohra ^{[6
]}

Meffre, Patrick ^{[6
]}

Kerr-Conte, Julie

Pattou, Francois

Froguel, Philippe ^{[1
,7
]}

Bonnefond, Amelie ^{[1
,7
]}

Oger, Frederik ^{[1
]}

Annicotte, Jean-Sebastien ^{[1
,2
]}

机构：

[1] Univ Lille, CNRS, Inst Pasteur Lille, INSERM,U1283,UMR 8199 EGID, F-59000 Lille, France

[2] Univ Lille, Inst Pasteur Lille, INSERM, CHU Lille,Fac Risque & Dterminants Mole Maladies, F-59000 Lille, France

[3] Univ Lille, Inst Pasteur Lille, INSERM, CHU Lille, F-59000 Lille, France

[4] Boston Univ, Dept Biochem, Sch Med, Boston, MA 02118 USA

[5] Univ prime Lille, INSERM, CHU Lille, U1172 LilNCog Lille Neuroscience Cognit EGID DIST, F-59000 Lille, France

[6] Univ Nimes, UPR CHROME, F-300211 Nimes 1, France

[7] Imperial Coll London, Hammersmith Hosp, Dept Metab, London W12 0NN, England

来源：

CELL REPORTS | 2022年 / 40卷 / 06期

关键词：

GLUCAGON-LIKE PEPTIDE-1; CYCLIN D1; EXPRESSION; PROLIFERATION; INDUCTION; EXENDIN-4; HORMONE; ACTIVATION; PROTEIN; HYPERGLYCEMIA;

D O I：

10.1016/j.celrep.2022.111170

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 bymodulating 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 b cell function and suggest molecular crosstalk between the E2F1/pRb and GLP1R signaling pathways.

引用

页数：17

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