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The cell regeneration phenomenon describes the process in which functional cells begin to proliferate to compensate for the loss. The perfect examples are the skin, the liver, the organs that repair themselves after damage.
For three decades, scientists have been examining the regenerative potential of beta cells, the pancreatic cells responsible for producing insulin.
The beta cell population is partially destroyed when diabetes occurs, and the recovery of these cells presents a unique clinical challenge.
In a new study from the University of Geneva and the University Hospitals of Geneva (HUG), scientists studied diabetic mice to observe the regeneration mechanism. They observed that this regeneration mechanism was under the influence of circadian rhythms – the molecular clocks that regulate metabolic functions in a 24-hour day-night cycle.
Scientists also identified the significant role of the central clock component BMAL1 in this process.
To explore the connection between internal biological clocks and beta cell regeneration, the scientists first observed two groups of mice with only 20% remaining beta cells after massive targeted ablation. The mice in the first group were arrhythmic, while the control group had perfectly functioning clocks.
Volodymyr Petrenko, a researcher in Dr. Dibner’s lab and lead scientist in this study, said: “The result was very clear: the mice with dysfunctional clocks were unable to regenerate their beta cells and suffered from severe diabetes, while the control animals had regenerated their beta cells; within weeks their diabetes was under control. By measuring the number of dividing beta cells in 24 hours, the scientists also noted that regeneration is significantly greater at night when the mice are active. “
“Arrhythmic mice lacked the BMAL1 gene, which codes for the protein of the same name, a transcription factor known for its key activities in the functioning of the circadian clock. Our analyzes show that the BMAL1 gene is essential for the regeneration of beta cells. “
“Furthermore, large-scale transcriptomic analyzes over 24 hours, conducted in collaboration with Prof. Bart Vandereycken at UNIGE’s Department of Mathematics, revealed that the genes responsible for cell cycle regulation and proliferation were not alone. upregulated, but they have also acquired circadian rhythmicity “.
Charna Dibner, head of the Circadian Endocrinology Laboratory at the Departments of Medicine, Cellular Physiology and Metabolism of the UNIGE Faculty of Medicine, said: “BMAL1 appears to be really central to our investigation. However, it is unclear whether regeneration requires the same functional circadian clocks, or just BMAL1, whose range of functions extends beyond clocks. This is what we would like to find out at the moment. “
Scientists also want to explore the function of alpha cells, which produce glucagon, the hormone that antagonizes insulin, in this model. The arrhythmic mice showed very high levels of glucagon in the blood. A detailed understanding of these mechanisms now needs to be pursued in an attempt to explore the possibility of triggering beta cell regeneration in humans in the future. “
These results, to be read in the journal Gene and Development, allow us to predict new perspectives for promoting beta cell regeneration.
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