- Brown, Matthew R;
- Sen, Satish K;
- Mazzone, Amelia;
- Her, Tracy K;
- Xiong, Yuning;
- Lee, Jeong-Heon;
- Javeed, Naureen;
- Colwell, Christopher S;
- Rakshit, Kuntol;
- LeBrasseur, Nathan K;
- Gaspar-Maia, Alexandre;
- Ordog, Tamas;
- Matveyenko, Aleksey V
Circadian rhythm disruption (CD) is associated with impaired glucose homeostasis and type 2 diabetes mellitus (T2DM). While the link between CD and T2DM remains unclear, there is accumulating evidence that disruption of fasting/feeding cycles mediates metabolic dysfunction. Here, we used an approach encompassing analysis of behavioral, physiological, transcriptomic, and epigenomic effects of CD and consequences of restoring fasting/feeding cycles through time-restricted feeding (tRF) in mice. Results show that CD perturbs glucose homeostasis through disruption of pancreatic β cell function and loss of circadian transcriptional and epigenetic identity. In contrast, restoration of fasting/feeding cycle prevented CD-mediated dysfunction by reestablishing circadian regulation of glucose tolerance, β cell function, transcriptional profile, and reestablishment of proline and acidic amino acid–rich basic leucine zipper (PAR bZIP) transcription factor DBP expression/activity. This study provides mechanistic insights into circadian regulation of β cell function and corresponding beneficial effects of tRF in prevention of T2DM.