325-LB: Circadian Clock Nuclear Receptor REV-ERBa Is a Novel Regulator of Beta-Cell Function, Survival, and Autophagy under Diabetogenic Conditions

Autor: Damien Laouteouet, Magalie A. Ravier, Aleksey V. Matveyenko, Morgane Delobel, Gyslaine Bertrand, Stephane Dalle, Safia Costes
Rok vydání: 2019
Předmět:
Zdroj: Diabetes. 68
ISSN: 1939-327X
0012-1797
Popis: The circadian clock regulates diverse cellular and molecular rhythms employing CLOCK-BMAL1 transcriptional heterodimer with nuclear receptor REV-ERBα (encoded by gene Nr1d1) playing an important role as a clock repressor through modulation of Bmal1 transcription. Importantly, in addition to its core circadian clock function, recent studies have identified REV-ERBα as a potent transcriptional repressor of autophagy. Therefore, in the current study we set out to address whether impaired beta-cell function and survival associated with exposure to diabetogenic stressors (e.g., glucotoxicity and inflammation) is attributed in part to REV-ERBα-mediated inhibition of autophagy. Exposure of beta-cells (INS-1E cell line) to either glucotoxicity (30 mM glucose) or cytokines (cytomix of IL-1β, TNFα and IFNγ) resulted in robust induction of REV-ERBα expression (1.5-2 fold, p Disclosure S. Costes: None. D. Laouteouet: None. M.A. Ravier: None. M. Delobel: None. G. Bertrand: None. S. Dalle: None. A. Matveyenko: None.
Databáze: OpenAIRE