1. The core clock transcription factor BMAL1 drives circadian β-cell proliferation during compensatory regeneration of the endocrine pancreas.
- Author
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Petrenko V, Stolovich-Rain M, Vandereycken B, Giovannoni L, Storch KF, Dor Y, Chera S, and Dibner C
- Subjects
- Animals, Cell Proliferation genetics, Circadian Rhythm, Glucagon-Secreting Cells cytology, Mice, Transcriptome, ARNTL Transcription Factors genetics, ARNTL Transcription Factors metabolism, Insulin-Secreting Cells cytology, Pancreas physiology, Regeneration genetics
- Abstract
Circadian clocks in pancreatic islets participate in the regulation of glucose homeostasis. Here we examined the role of these timekeepers in β-cell regeneration after the massive ablation of β cells by doxycycline-induced expression of diphtheria toxin A (DTA) in Insulin-rtTA/TET-DTA mice. Since we crossed reporter genes expressing α- and β-cell-specific fluorescent proteins into these mice, we could follow the fate of α- and β cells separately. As expected, DTA induction resulted in an acute hyperglycemia, which was accompanied by dramatic changes in gene expression in residual β cells. In contrast, only temporal alterations of gene expression were observed in α cells. Interestingly, β cells entered S phase preferentially during the nocturnal activity phase, indicating that the diurnal rhythm also plays a role in the orchestration of β-cell regeneration. Indeed, in arrhythmic Bmal1 -deficient mice, which lack circadian clocks, no compensatory β-cell proliferation was observed, and the β-cell ablation led to aggravated hyperglycemia, hyperglucagonemia, and fatal diabetes., (© 2020 Petrenko et al.; Published by Cold Spring Harbor Laboratory Press.)
- Published
- 2020
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