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The transcriptional co\u2010activator PGC\u20101\u03b1 regulates muscle oxidative phenotype which has been shown to be linked with basal autophagic capacity. Therefore, young and aged inducible muscle\u2010specific PGC\u20101\u03b1 knockout (iMKO) mice and littermate lox\/lox controls were used in three separate experiments performed after either saline or colchicine injections on two consecutive days: (1) Euthanization in the basal state obtaining skeletal muscle for mitochondrial respirometry, (2) whole body glucose tolerance test, and (3) in vivo insulin\u2010stimulated 2\u2010deoxyglucose (2\u2010DG) uptake into skeletal muscle. Muscle PGC\u20101\u03b1 was not required for maintaining basal autophagy flux, regardless of age. Colchicine\u2010induced inhibition of autophagy was associated with impairments of skeletal muscle mitochondrial function, including reduced ADP sensitivity and altered mitochondrial redox balance in both young and aged mice. Colchicine treatment reduced the glucose tolerance in aged, but not young mice, and similarly in iMKO and lox\/lox mice. Colchicine reduced insulin\u2010stimulated 2\u2010DG uptake in soleus muscle in aged mice, independently of PGC\u20101\u03b1, and without affecting insulin\u2010regulated phosphorylation of proximal or distal mediators of insulin signaling. In conclusion, the results indicate that autophagy regulates the mitochondrial ADP sensitivity and redox balance as well as whole body glucose tolerance and skeletal muscle insulin sensitivity in aged mice, with no additional effects of inducible PGC\u20101\u03b1 deletion.<\/jats:p>","DOI":"10.1096\/fj.201903113rr","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T23:58:55Z","timestamp":1588723135000},"page":"8653-8670","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Colchicine treatment impairs skeletal muscle mitochondrial function and insulin sensitivity in an age\u2010specific manner"],"prefix":"10.1096","volume":"34","author":[{"given":"Bj\u00f8rg Thiellesen","family":"Buch","sequence":"first","affiliation":[{"name":"Department of Biology University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens Frey","family":"Halling","sequence":"additional","affiliation":[{"name":"Department of Biology University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine","family":"Ringholm","sequence":"additional","affiliation":[{"name":"Department of Biology University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Gudiksen","sequence":"additional","affiliation":[{"name":"Department of Biology University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasmus","family":"Kj\u00f8bsted","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Exercise and Sports University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette Algot","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Biology University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rgen F. 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