Abstract Introduction Sleep is essential for maintaining metabolic homeostasis. Disruptions in sleep and circadian rhythms adversely affect glucose metabolism and hormonal regulation, thereby promotes the development of metabolic syndrome. In individuals with diabetes mellitus, sleep disturbances are frequently observed and often attributed to secondary complications such as nocturia; however, the common co-occurrence of hyperglycemia and impaired sleep indicates a complex bidirectional relationship. Despite accumulating evidence delineating the interplay between metabolic state and sleep physiology, the mechanistic pathways through which acute hyperglycemia directly influences sleep architecture remain inadequately characterized. Methods Acute hyperglycemia was induced in C57BL/6 mice by 8-hour fasting followed by intraperitoneal diazoxide injection and oral glucose gavage, producing ~6 h of elevated blood glucose. EEG/EMG recordings were acquired during this period, with DMSO- and saline-treated mice as controls. For immunohistochemistry, mice (n = 3/group) were sacrificed 3 h after treatment, perfused with PBS and 4% paraformaldehyde, cryoprotected, sectioned (40 μm), and stained with anti-NeuN and anti-c-Fos antibodies. c-Fos+/NeuN+ neurons were quantified. To monitor locus coeruleus (LC) activity, a TH-Cre mouse received AAV(DJ)-EF1a-DIO-GCaMP6f injection into the right LC and optic fiber implantation 0.15 mm above the site, followed by simultaneous EEG/EMG and fiber photometry. Results Acute hyperglycemia markedly suppressed REM sleep, reducing REM percentage, bout length, and duration. EEG absolute power decreased across wake and NREM, indicating dampened cortical activity. Acute hyperglycemia selectively reduced NREM sleep spindle amplitude while leaving spindle density unchanged, suggesting intact initiation but weakened thalamocortical synchrony. LC fiber photometry and c-Fos staining showed increased noradrenergic LC activity during NREM after diazoxide. Conclusion Acute hyperglycemia directly suppresses REM sleep, reduces cortical activation, and weakens thalamocortical synchrony, with LC hyperactivity mediating REM inhibition. This study provides the first experimental evidence that a transient elevation in glucose is sufficient to rapidly disrupt REM sleep through LC activation, revealing a metabolic–neuromodulatory mechanism linking hyperglycemia to impaired sleep regulation. Support (if any) Ministry of Health & Welfare, South Korea (HI22C0467).
Baniya et al. (Fri,) studied this question.