ArticleThe Journal of biological chemistry2010
Impaired glucose tolerance and predisposition to the fasted state in liver glycogen synthase knock-out mice.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 90 citations in OpenAlex.
- Article
- Glycogen metabolic dysfunction in T2DM with MASLD: linking α-hydroxybutyrate to GYS2 downregulation.Frontiers in nutrition · 2026Article
- Fasting-Induced Hepatic Gluconeogenesis Is Compromised In Anxa6Journal of cellular physiology · 2025Article
- Hepatic glycogen directly regulates gluconeogenesis through an AMPK/CRTC2 axis in mice.The Journal of clinical investigation · 2025Article
- Article
- Single-Atom Ce-N-C Nanozyme Ameliorates Type 2 Diabetes Mellitus by Improving Glucose Metabolism Disorders and Reducing Oxidative Stress.Biomolecules · 2024Article
- Neuron-astrocyte metabolic coupling facilitates spinal plasticity and maintenance of inflammatory pain.Nature metabolism · 2024Article
- mTORC1 controls murine postprandial hepatic glycogen synthesis via Ppp1r3b.The Journal of clinical investigation · 2024Article
- Microbiota influences host exercise capacity via modulation of skeletal muscle glucose metabolism in mice.Experimental & molecular medicine · 2023Article
- Dendropanoxide Alleviates Thioacetamide-induced Hepatic Fibrosis via Inhibition of ROS Production and Inflammation in BALB/International journal of biological sciences · 2023Article
- Disruption of the circadian clock component BMAL1 elicits an endocrine adaption impacting on insulin sensitivity and liver disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Hydroxy-α-sanshool isolated fromFrontiers in pharmacology · 2022Article
- Insulin-Related Liver Pathways and the Therapeutic Effects of Aerobic Training, Green Coffee, and Chlorogenic Acid Supplementation in Prediabetic Mice.Oxidative medicine and cellular longevity · 2022Article
- Disrupting AMPK-Glycogen Binding in Mice Increases Carbohydrate Utilization and Reduces Exercise Capacity.Frontiers in physiology · 2022Article
- Gene Expression Profiling of Skeletal Muscles.Genes · 2021Article
- Short-chain fatty acids can improve lipid and glucose metabolism independently of the pig gut microbiota.Journal of animal science and biotechnology · 2021Article
- The Source of Glycolytic Intermediates in Mammalian Tissues.Cell metabolism · 2021Article
- Maintenance of liver glycogen during long-term fasting preserves energy state in mice.FEBS letters · 2020Article
- Discovery and Development of Small-Molecule Inhibitors of Glycogen Synthase.Journal of medicinal chemistry · 2020Article
- Maternal cinnamon intake during lactation led to visceral obesity and hepatic metabolic dysfunction in the adult male offspring.Endocrine · 2019Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Conversion to glycogen is a major fate of ingested glucose in the body. A rate-limiting enzyme in the synthesis of glycogen is glycogen synthase encoded by two genes, GYS1, expressed in muscle and other tissues, and GYS2, primarily expressed in liver (liver glycogen synthase). Defects in GYS2 cause the inherited monogenic disease glycogen storage disease 0. We have generated mice with a liver-specific disruption of the Gys2 gene (liver glycogen synthase knock-out (LGSKO) mice), using Lox-P/Cre technology. Conditional mice carrying floxed Gys2 were crossed with mice expressing Cre recombinase under the albumin promoter. The resulting LGSKO mice are viable, develop liver glycogen synthase deficiency, and have a 95% reduction in fed liver glycogen content. They have mild hypoglycemia but dispose glucose less well in a glucose tolerance test. Fed, LGSKO mice also have a reduced capacity for exhaustive exercise compared with mice carrying floxed alleles, but the difference disappears after an overnight fast. Upon fasting, LGSKO mice reach within 4 h decreased blood glucose levels attained by control floxed mice only after 24 h of food deprivation. The LGSKO mice maintain this low blood glucose for at least 24 h. Basal gluconeogenesis is increased in LGSKO mice, and insulin suppression of endogenous glucose production is impaired as assessed by euglycemic-hyperinsulinemic clamp. This observation correlates with an increase in the liver gluconeogenic enzyme phosphoenolpyruvate carboxykinase expression and activity. This mouse model mimics the pathophysiology of glycogen storage disease 0 patients and highlights the importance of liver glycogen stores in whole body glucose homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.