Journal article
Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1) deletion in adult mice
CE Xirouchaki, SP Mangiafico, K Bate, Z Ruan, AM Huang, BW Tedjosiswoyo, B Lamont, W Pong, J Favaloro, AR Blair, JD Zajac, J Proietto, S Andrikopoulos
Molecular Metabolism | Published : 2016
Abstract
Objective: 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 ..
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Funding Acknowledgements
The authors would like to thank Alexandra Funkat, Blaise Henrich, Margaret Shaw, Lisa Billington, Rebecca Sgambellone and Yaelle Faulsen for their excellent technical assistance and contribution to the molecular and physiological characterisation of the model. This work was supported by Diabetes Australia Research Program and National Health and Medical Research Council of Australia Project Grant.