Hyperglycaemia reversibly disrupts circadian behaviour in mice
Disrupted sleep and circadian rhythms are among the most common features of diabetes, and are known to raise the risk of developing the disease. Whether the relationship also runs the other way, with diabetes itself disrupting the clock, has remained unresolved. Using an inducible mouse model of diabetes, in which hyperglycaemia can be induced and then reversed within the same animal, we show…
New research reveals that hyperglycaemia can temporarily disrupt circadian rhythms in mice, suggesting a bidirectional link between blood glucose levels and the body's internal clock. In an experiment using an inducible mouse model of diabetes, elevated blood glucose was found to decrease circadian rest-activity rhythms by half and shorten the free-running period of the clock, with these effects being directly proportional to the degree of hyperglycaemia.
Restoring normal glucose levels reversed these disruptions. Diabetic mice exhibited a delayed onset of activity, indicating a later chronotype, and showed slower re-entrainment after simulated jet lag. However, their phase shifting to nocturnal light pulses remained unaffected, implying normal photic responses. Additionally, both brain glucose levels and O-GlcNAcylation, a nutrient-sensitive protein modification, were elevated in diabetic animals, demonstrating that elevated peripheral glucose levels reach the brain and alter its metabolic state.
These findings establish that a peripheral metabolic state is a reversible determinant of circadian behavior, emphasizing the need to treat blood glucose and the clock together rather than separately.
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