["The Journal of Physiology, Volume 604, Issue 7, Page 2717-2737, 1 April 2026. ", "\nAbstract figure legend Contraction‐induced formation of a NET‐based immunometabolic niche potentiates regional insulin sensitivity and GLUT4 translocation.\nThe schematic model illustrating how skeletal muscle contraction promotes a NET‐based immunometabolic niche that enhances regional insulin sensitivity. Muscle contraction induces the release of myokines/exerkines (1), leading to neutrophil recruitment to the skeletal muscle microvasculature via CXCR2/CX3CR1 signalling (2). Recruited neutrophils form intravascular neutrophil extracellular traps (NETs) within the capillary network (3), which may alter the local perivascular microenvironment and insulin access. NET formation locally potentiates insulin signalling in adjacent myofibres, resulting in modest Akt (S473) and AS160/TBC1D4 (T642) phosphorylation and enhanced sarcolemmal GLUT4 accumulation. This spatially restricted immunometabolic niche provides a conceptual framework linking vascular immune responses to myofibre insulin action following muscle contraction.\n\n\n\n\n\n\n\n\n\nAbstract\nExercise is well known to enhance insulin sensitivity in skeletal muscle, yet the underlying mechanisms remain incompletely understood. We have previously shown that neutrophil recruitment contributes to contraction‐induced GLUT4 translocation and local myokine induction, but whether these immune cells also participate in the post‐exercise increase in insulin sensitivity has been unclear. Here using GLUT4‐EGFP transgenic mice and sciatic nerve‐mediated in situ contraction of the hindlimb, with analyses focused on extensor digitorum longus (EDL) muscle, we demonstrate that neutrophil recruitment and subsequent formation of neutrophil extracellular traps (NETs) are crucial for the well‐known post‐exercise increase in insulin sensitivity. Two‐photon imaging revealed that NET‐like cell‐free DNA (cfDNA) structures persisted for hours after contraction, forming spatially confined perivascular immunometabolic niches along the capillary meshwork. Strikingly insulin‐stimulated GLUT4 translocation was preferentially enriched at these NET‐rich sites, whereas DNase‐mediated NET degradation eliminated cfDNA signals and abolished the contraction‐induced enhancement of GLUT4 translocation, glucose uptake and attenuated AS160 (T642) phosphorylation under low‐dose insulin. Our findings demonstrate that neutrophils are essential components of the mechanism underlying enhanced post‐exercise insulin sensitivity involving, at least in part, the local formation of NETs. These NET‐governed immunometabolic niches constitute a structural and spatial framework underlying the exercise‐induced acute improvement of insulin‐responsive metabolic efficiency in skeletal muscle.\n\n\n\n\n\n\n\n\n\nKey points\n\nNeutrophil extracellular traps (NETs) establish spatially confined immunometabolic niches that are indispensable for the post‐exercise increase in insulin sensitivity.\nHigh‐resolution imaging revealed that insulin‐stimulated GLUT4 translocation is markedly enhanced predominantly in NET‐rich perivascular regions, indicating a spatially restricted mechanism of post‐exercise insulin sensitization.\nDNase‐mediated degradation of NETs abolished this enhancement, establishing their essential role in local insulin‐responsive GLUT4 translocation.\nThese NETs are formed by neutrophils rapidly recruited to skeletal muscle after contraction and deposited along the capillary network.\n\n\n"]