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In Duchenne muscular dystrophy, loss of dystrophin is associated with altered metabolic regulation. In the mdx mouse, we show that physiological stress reveals impaired coordination between insulin and stress responses: glucocorticoid signalling increases without a proportional rise in insulin secretion, resulting in systemic hyperglycaemia despite preserved capacity for muscle glucose uptake. These data support a multi-tissue dystrophinopathy associated with altered endocrine-metabolic coordination. Skeletal muscle glycogen is elevated and incompletely mobilised under stress. The heart maintains high glucose uptake, whereas the brain exhibits reduced uptake, highlighting tissue specific differences in metabolic response. Acute insulin supplementation improves systemic glucose control and restores stress-induced behavioural deficits. Likewise, empagliflozin-mediated glucose offloading reduces stress-associated blood glucose spikes and is associated with improved muscle function to levels comparable with standard care prednisolone. These findings identify impaired coordination of endocrine and metabolic responses during stress as a contributor to metabolic vulnerability in DMD and suggest that modulating insulin availability or glucose flux can improve systemic metabolic control.<\/jats:p>","DOI":"10.64898\/2026.02.22.707291","type":"posted-content","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T04:15:12Z","timestamp":1771906512000},"source":"Crossref","is-referenced-by-count":1,"title":["Stress unmasks impaired endocrine coordination of glucose metabolism in dystrophin deficiency"],"prefix":"10.64898","author":[{"given":"Gretel S","family":"Major","sequence":"first","affiliation":[{"name":"School of Biological Sciences, University of Canterbury, Christchurch 8041, New Zealand"},{"name":"Biomolecular Interaction Centre, School of Biological Sciences, University of Canterbury, Christchurch 8140, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara A.","family":"Timpani","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne, Victoria 8001, Australia"},{"name":"Australian Institute for Musculoskeletal Science (AIMSS), Victoria University and Western Health, St Albans, Victoria 3021, Australia"},{"name":"Department of Medicine\u2014Western Health, Melbourne Medical School, The University of Melbourne, St Albans, Victoria 3021, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Lalunio","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne, Victoria 8001, Australia"},{"name":"Australian Institute for Musculoskeletal Science (AIMSS), Victoria University and Western Health, St Albans, Victoria 3021, Australia"},{"name":"Department of Medicine\u2014Western Health, Melbourne Medical School, The University of Melbourne, St Albans, Victoria 3021, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Canterbury, Christchurch 8041, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Boatner","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition, Foods, and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA"},{"name":"Metabolism Core, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Giourmas","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne, Victoria 8001, Australia"},{"name":"Australian Institute for Musculoskeletal Science (AIMSS), Victoria University and Western Health, St Albans, Victoria 3021, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Kourakis","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne, Victoria 8001, Australia"},{"name":"Australian Institute for Musculoskeletal Science (AIMSS), Victoria University and Western Health, St Albans, Victoria 3021, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"van den Berg","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Canterbury, Christchurch 8041, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Salimova","sequence":"additional","affiliation":[{"name":"Monash Biomedical Imaging, Monash University, Clayton, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Eliades","sequence":"additional","affiliation":[{"name":"Monash Metabolic Phenotyping Platform, Monash Biomedicine Discovery Institute, Monash University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Monash Biomedical Imaging, Monash University, Clayton, Victoria 3800, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, Victoria 3004, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukhvir Kaur","family":"Bhangu","sequence":"additional","affiliation":[{"name":"Department of Diabetes, School of Translational Medicine, Monash University, Melbourne, Victoria 3004, Australia."},{"name":"Department of Chemical Engineering, The University of Melbourne, Parkville, Victoria 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thirimadura V. 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