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dc.contributor.authorXirouchaki, CE
dc.contributor.authorMangiafico, SP
dc.contributor.authorBate, K
dc.contributor.authorRuan, Z
dc.contributor.authorHuang, AM
dc.contributor.authorTedjosiswoyo, BW
dc.contributor.authorLamont, B
dc.contributor.authorPong, W
dc.contributor.authorFavaloro, J
dc.contributor.authorBlair, AR
dc.contributor.authorZajac, JD
dc.contributor.authorProietto, J
dc.contributor.authorAndrikopoulos, S
dc.date.accessioned2020-12-22T05:44:10Z
dc.date.available2020-12-22T05:44:10Z
dc.date.issued2016-03-01
dc.identifierpii: S2212-8778(16)00014-4
dc.identifier.citationXirouchaki, C. E., Mangiafico, S. P., Bate, K., Ruan, Z., Huang, A. M., Tedjosiswoyo, B. W., Lamont, B., Pong, W., Favaloro, J., Blair, A. R., Zajac, J. D., Proietto, J. & Andrikopoulos, S. (2016). Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1) deletion in adult mice. MOLECULAR METABOLISM, 5 (3), pp.221-232. https://doi.org/10.1016/j.molmet.2016.01.004.
dc.identifier.issn2212-8778
dc.identifier.urihttp://hdl.handle.net/11343/258347
dc.description.abstractOBJECTIVE: Muscle glucose storage and muscle glycogen synthase (gys1) defects have been associated with insulin resistance. As there are multiple mechanisms for insulin resistance, the specific role of glucose storage defects is not clear. The aim of this study was to examine the effects of muscle-specific gys1 deletion on glucose metabolism and exercise capacity. METHODS: Tamoxifen inducible and muscle specific gys-1 KO mice were generated using the Cre/loxP system. Mice were subjected to glucose tolerance tests, euglycemic/hyperinsulinemic clamps and exercise tests. RESULTS: gys1-KO mice showed ≥85% reduction in muscle gys1 mRNA and protein concentrations, 70% reduction in muscle glycogen levels, postprandial hyperglycaemia and hyperinsulinaemia and impaired glucose tolerance. Under insulin-stimulated conditions, gys1-KO mice displayed reduced glucose turnover and muscle glucose uptake, indicative of peripheral insulin resistance, as well as increased plasma and muscle lactate levels and reductions in muscle hexokinase II levels. gys1-KO mice also exhibited markedly reduced exercise and endurance capacity. CONCLUSIONS: Thus, muscle-specific gys1 deletion in adult mice results in glucose intolerance due to insulin resistance and reduced muscle glucose uptake as well as impaired exercise and endurance capacity. IN BRIEF: This study demonstrates why the body prioritises muscle glycogen storage over liver glycogen storage despite the critical role of the liver in supplying glucose to the brain in the fasting state and shows that glycogen deficiency results in impaired glucose metabolism and reduced exercise capacity.
dc.languageEnglish
dc.publisherELSEVIER SCIENCE BV
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.titleImpaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1) deletion in adult mice
dc.typeJournal Article
dc.identifier.doi10.1016/j.molmet.2016.01.004
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.affiliation.departmentMedicine (Austin & Northern Health)
melbourne.affiliation.departmentMedicine (RMH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleMolecular Metabolism
melbourne.source.volume5
melbourne.source.issue3
melbourne.source.pages221-232
dc.rights.licenseCC BY-NC-ND
melbourne.elementsid1041125
melbourne.contributor.authorRuan, Zheng
melbourne.contributor.authorProietto, Joseph
melbourne.contributor.authorZajac, Jeffrey
melbourne.contributor.authorMangiafico, Salvatore
melbourne.contributor.authorAndrikopoulos, Sofianos
melbourne.contributor.authorHuang, Mengjie
melbourne.contributor.authorBATE, KATHERINE
melbourne.contributor.authorTEDJOSISWOYO, BING
melbourne.contributor.authorLAMONT, BENJAMIN
melbourne.contributor.authorPONG, WYNNE
melbourne.contributor.authorFAVALORO, JENNY
melbourne.contributor.authorBLAIR, AMY
melbourne.contributor.authorXirouchaki, Chrysovalantou Eleni
dc.identifier.eissn2212-8778
melbourne.accessrightsOpen Access


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