{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T15:17:11Z","timestamp":1784387831571,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K02874"],"award-info":[{"award-number":["24K02874"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"\n Abstract<\/jats:title>\n \n Exercise 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\u2010induced GLUT4 translocation and local myokine induction, but whether these immune cells also participate in the post\u2010exercise increase in insulin sensitivity has been unclear. Here using GLUT4\u2010EGFP transgenic mice and sciatic nerve\u2010mediated\n in situ<\/jats:italic>\n 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\u2010known post\u2010exercise increase in insulin sensitivity. Two\u2010photon imaging revealed that NET\u2010like cell\u2010free DNA (cfDNA) structures persisted for hours after contraction, forming\u00a0spatially confined perivascular immunometabolic niches\u00a0along the capillary meshwork. Strikingly insulin\u2010stimulated GLUT4 translocation was\u00a0preferentially enriched at these NET\u2010rich sites, whereas DNase\u2010mediated NET degradation eliminated cfDNA signals and\u00a0abolished the contraction\u2010induced enhancement of GLUT4 translocation, glucose uptake and attenuated AS160 (T642) phosphorylation\u00a0under low\u2010dose insulin. Our findings demonstrate that neutrophils are essential components of the mechanism underlying enhanced post\u2010exercise insulin sensitivity involving, at least in part, the local formation of NETs. These NET\u2010governed immunometabolic niches constitute a structural and spatial framework underlying the exercise\u2010induced acute improvement of insulin\u2010responsive metabolic efficiency in skeletal muscle.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Neutrophil extracellular traps (NETs) establish spatially confined immunometabolic niches that are indispensable for the post\u2010exercise increase in insulin sensitivity.<\/jats:p>\n <\/jats:list-item>\n \n High\u2010resolution imaging revealed that insulin\u2010stimulated GLUT4 translocation is markedly enhanced predominantly in NET\u2010rich perivascular regions, indicating a spatially restricted mechanism of post\u2010exercise insulin sensitization.<\/jats:p>\n <\/jats:list-item>\n \n DNase\u2010mediated degradation of NETs abolished this enhancement, establishing their essential role in local insulin\u2010responsive GLUT4 translocation.<\/jats:p>\n <\/jats:list-item>\n \n These NETs are formed by neutrophils rapidly recruited to skeletal muscle after contraction and deposited along the capillary network.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp290203","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:24:51Z","timestamp":1773005091000},"page":"2717-2737","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intramuscular neutrophil\u2010derived immunometabolic niches locally boost insulin\u2010responsive GLUT4 translocation after muscle contraction"],"prefix":"10.1113","volume":"604","author":[{"given":"Weijian","family":"Chen","sequence":"first","affiliation":[{"name":"Graduate School of Biomedical Engineering Tohoku University Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6884-2955","authenticated-orcid":false,"given":"Makoto","family":"Kanzaki","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Engineering Tohoku University Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40279-014-0296-1"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2818.2006.01706.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2006.01.005"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00416.2015"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1989.256.4.E494"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/joa.13339"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP278564"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200101)31:1<265::AID-IMMU265>3.0.CO;2-L"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48316-9"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0143635"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14075"},{"issue":"22","key":"e_1_2_5_14_1","article-title":"Glucocorticoid chronopharmacology promotes glucose metabolism in heart through a cardiomyocyte\u2010autonomous transactivation program","volume":"9","author":"Durumutla H. 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