The core clock transcription factor BMAL1 drives circadian β-cell proliferation during compensatory regeneration of the endocrine pancreas.

TitleThe core clock transcription factor BMAL1 drives circadian β-cell proliferation during compensatory regeneration of the endocrine pancreas.
Publication TypeJournal Article
Year of Publication2020
AuthorsPetrenko V, Stolovich-Rain M, Vandereycken B, Giovannoni L, Storch K-F, Dor Y, Chera S, Dibner C
JournalGenes Dev
Volume34
Issue23-24
Pagination1650-1665
Date Published2020 Dec 01
ISSN1549-5477
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 -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.

DOI10.1101/gad.343137.120
Alternate JournalGenes Dev
PubMed ID33184223
PubMed Central IDPMC7706703