ArticleMolecular metabolism2016
Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1) deletion in adult mice.
Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- Disulfidptosis-Induced Chondrocyte-Macrophage Crosstalk via GYS1/CCND1/NOD2 Axis Promotes Osteoarthritis Progression.Journal of inflammation research · 2026Article
- IUGR remodels glycogen synthesis in CG-IUGR rats.Endocrine connections · 2025Article
- Screening of key genes related to disulfidptosis in psoriasis based on the analysis of WGCNA.Scientific reports · 2025Article
- Skeletal muscle disorders as risk factors for type 2 diabetes.Molecular and cellular endocrinology · 2025Review
- Combined Effects of Spirulina Liquid Extract and Endurance Training on Aerobic Performance and Muscle Metabolism Adaptation in Wistar Rats.Nutrients · 2025Article
- A novel CD71 Centyrin:Gys1 siRNA conjugate reduces glycogen synthesis and glycogen levels in a mouse model of Pompe disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Genetic reduction of skeletal muscle glycogen synthase 1 abundance reveals that the refeeding-induced reversal of elevated insulin-stimulated glucose uptake after exercise is not attributable to achieving a high muscle glycogen concentration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Targeting Disulfidptosis with Potentially Bioactive Natural Products in Metabolic Cancer Therapy.Metabolites · 2024Review
- Effects of Different Photoperiods on Peripheral 5-Hydroxytryptamine Metabolism, Breast Muscle Glucose Metabolism, and Myopathies in Broilers.Metabolites · 2024Article
- Small molecule inhibition of glycogen synthase I reduces muscle glycogen content and improves biomarkers in a mouse model of Pompe disease.American journal of physiology. Endocrinology and metabolism · 2024Article
- Exogenous Lactate Treatment Immediately after Exercise Promotes Glycogen Recovery in Type-II Muscle in Mice.Nutrients · 2024Article
- Article
- Integrating miRNA and full-length transcriptome profiling to elucidate the mechanism of muscle growth in Muscovy ducks reveals key roles for miR-301a-3p/ANKRD1.BMC genomics · 2024Article
- Small-molecule inhibition of glycogen synthase 1 for the treatment of Pompe disease and other glycogen storage disorders.Science translational medicine · 2024Article
- MicroRNA-92b in the skeletal muscle regulates exercise capacity via modulation of glucose metabolism.Journal of cachexia, sarcopenia and muscle · 2023Article
- Review
- Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging.Protein & cell · 2023Article
- The Pathogenesis of Diabetes.International journal of molecular sciences · 2023Review
- Plasma Exosomal miRNAs Associated With Metabolism as Early Predictor of Gestational Diabetes Mellitus.Diabetes · 2022Article
- Cystine/Glutamine Mixture Supplementation Attenuated Fatigue during Endurance Exercise in Healthy Young Men by Enhancing Fatty Acid Utilization.Sports (Basel, Switzerland) · 2022Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveMuscle 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.
methodsTamoxifen 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.
resultsgys1-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.
conclusionsThus, 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.
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