Glucose is dynamically regulated by time of day in humans and Drosophila

Apr 16, 2026PLoS biology

Daily changes in glucose levels in humans and fruit flies

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Circadian Biology on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

A pronounced 'rush hour' of glucose utilization occurs early in the light phase in Drosophila.

Daily oscillations in glucose-derived metabolic networks were identified using human metabolomics and isotope tracing.
In Drosophila, glucose is directed into biosynthetic and energetic pathways during peak utilization.
A hyperactive mutant showed shifted and amplified metabolic peaks, suggesting altered neural signaling affects glucose processing.
Circadian timing appears to regulate intrinsic metabolic rhythms, independent of feeding schedules or short-term fasting.
The study defines a conserved temporal pattern of glucose utilization, linking circadian misalignment to metabolic dysfunction.

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Biological clocks shape metabolism, but how circadian programs govern nutrient processing is unclear. Here, using human metabolomics and 13C6-glucose tracing in Drosophila, we delineate previously under characterized daily oscillations in glucose-derived metabolic networks, providing a mechanistic framework for a purpose-built isotope-tracing approach. In flies, we reveal a pronounced "rush hour" of glucose utilization early in the light phase, with carbons directed to biosynthetic and energetic pathways. By contrast, a dopamine reuptake-deficient hyperactive mutant (fumin) with elevated metabolic rate shows phase-shifted and amplified metabolic peaks, indicating that altered neural signaling reshapes temporal glucose flux. Neither altered feeding schedules nor short-term fasting disrupt these intrinsic metabolic rhythms, strongly suggesting that circadian timing, rather than nutrient availability, orchestrates temporal homeostasis. By integrating human metabolite profiling with isotope-tracing in flies, we define a conserved temporal architecture of glucose utilization and demonstrate that metabolic flux is dynamically gated across the day. Our findings establish a framework for understanding how circadian misalignment contributes to metabolic dysfunction and disease.

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Glucose is dynamically regulated by time of day in humans and Drosophila

Abstract

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