Injury size regulates glucose allocation locally and systemically during vertebrate tissue regeneration
- 1Hubrecht Institute
Abstract
Tissue regeneration requires careful allocation of metabolic resources, yet how organisms adjust this allocation in response to varying amounts of tissue loss remains poorly understood. Here, we show that the regenerative metabolic response is not fixed: the size of an injury regulates how glucose is allocated at both local and organism-wide levels. We first demonstrate that tail regeneration requires glucose metabolism in the axolotl (Ambystoma mexicanum), a salamander capable of regenerating centimetre-scale tissues. We then mapped glucose uptake in axolotls regenerating from small or large tail injuries using positron emission tomography/magnetic resonance imaging (PET/MRI) and the radiolabelled glucose analogue [18F]FDG. Glucose uptake was elevated in regenerating tails compared to uninjured tails. During early regeneration, larger injuries induced higher glucose uptake than smaller injuries, correlating with faster regenerative outgrowth. Larger injuries also increased glucose uptake in distant organs, indicating a systemic metabolic response. Together, our findings suggest that metabolic responses tuned to injury size underlie faithful tissue regeneration and establish PET/MRI as a powerful approach for studying whole-body metabolic dynamics in large regenerating vertebrates.
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BibTeX
@misc{kuntner2026injury,
title = {{Injury size regulates glucose allocation locally and systemically during vertebrate tissue regeneration}},
author = {C. Kuntner and C. Philippe and C. Vraka and L. Zachhuber and T. Wanek and J. Friske and V. Weissenboeck and T. Helbich and M. Hacker and E. Tanaka and L. Otsuki},
howpublished = {bioRxiv},
year = {2026},
month = aug,
doi = {10.64898/2026.08.31.748065},
url = {https://www.biorxiv.org/content/10.64898/2026.08.31.748065v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Injury size regulates glucose allocation locally and systemically during vertebrate tissue regeneration
AU - C. Kuntner
AU - C. Philippe
AU - C. Vraka
AU - L. Zachhuber
AU - T. Wanek
AU - J. Friske
AU - V. Weissenboeck
AU - T. Helbich
AU - M. Hacker
AU - E. Tanaka
AU - L. Otsuki
PY - 2026
DA - 2026/08/31
PB - bioRxiv
DO - 10.64898/2026.08.31.748065
UR - https://www.biorxiv.org/content/10.64898/2026.08.31.748065v1
AB - Tissue regeneration requires careful allocation of metabolic resources, yet how organisms adjust this allocation in response to varying amounts of tissue loss remains poorly understood. Here, we show that the regenerative metabolic response is not fixed: the size of an injury regulates how glucose is allocated at both local and organism-wide levels. We first demonstrate that tail regeneration requires glucose metabolism in the axolotl (Ambystoma mexicanum), a salamander capable of regenerating centimetre-scale tissues. We then mapped glucose uptake in axolotls regenerating from small or large tail injuries using positron emission tomography/magnetic resonance imaging (PET/MRI) and the radiolabelled glucose analogue [18F]FDG. Glucose uptake was elevated in regenerating tails compared to uninjured tails. During early regeneration, larger injuries induced higher glucose uptake than smaller injuries, correlating with faster regenerative outgrowth. Larger injuries also increased glucose uptake in distant organs, indicating a systemic metabolic response. Together, our findings suggest that metabolic responses tuned to injury size underlie faithful tissue regeneration and establish PET/MRI as a powerful approach for studying whole-body metabolic dynamics in large regenerating vertebrates.
ER -