Cited by 90Metabolism, Diabetes, and CancerGlycogen Storage Diseases and MyoclonusDiabetes, Cardiovascular Risks, and Lipoproteins

Regulation of muscle glycogen synthase phosphorylation and kinetic properties by insulin, exercise, adrenaline and role in insulin resistance

Jensen, Jørgen, Lai, Yu-Chiang·2009·Archives of Physiology and Biochemistry

Abstract

In mammals, excess carbohydrate is stored as glycogen and glycogen synthase is the enzyme that incorporates glucose units into the glycogen particle. Glycogen synthase activity is regulated by phosphorylation and allosterically activated by glucose 6-phosphate. Phosphorylation of nine serines by different kinases regulates glycogen synthase affinity for glucose 6-phosphate and its substrate UDP-glucose. Glucose 6-phosphate increases both enzyme activity and substrate affinity. Insulin and exercise increase glycogen synthase affinity for glucose 6-phosphate and activity whereas high glycogen content and adrenaline decrease affinity for glucose 6-phosphate and activity. However, insulin, exercise and adrenaline also regulate intracellular concentration of glucose 6-phosphate which will influence in vivo glycogen synthase activity. Importantly, type 2 diabetes is associated with reduced insulin-stimulated glycogen synthase activation. The nine phosphorylation sites theoretically allow 512 combinations of phosphorylation configurations of glycogen synthase with different kinetic properties. However, due to hierarchal phosphorylation, the number of configurations in vivo is most likely much lower. Unfortunately, many studies only report data on glycogen synthase activity measured with high concentration of UDP-glucose which holds back information about changes in substrate affinity. In this paper we discuss the physiological regulation of glycogen synthase phosphorylation and how the phosphorylation pattern regulates glycogen synthase kinetic properties.

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Crossref · 10.1080/13813450902778171

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  • GS is phosphorylated on at least nine sites and insulin and contraction dephosphorylates both C- and N terminal sites.

    “GS is phosphorylated on at least nine sites and insulin and contraction dephosphorylates both C- and N terminal sites [126].”

    From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [126]

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Authors
Jensen, J., & Lai, Y.-C.
Affiliations
National Institute of Occupational Health (NO)
Corresponding author
Jensen, Jørgen
Venue
Archives of Physiology and Biochemistry
Published
2009-02
Volume
115
Issue
1
Pages
13-21
ISSN
  • 0778-3124 (ISSN-L)
  • 1381-3455
  • 1744-4160
OpenAlex
W2153133153
Cited by
90
References
55
Citations by year
2025: 2 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 10 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 9
FWCI
4.02
Type
journal article
Language
en
Open access
closed
Locations
  • Archives of Physiology and Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders
Novo Nordisk Fonden
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
glycogen synthase, phosphorylation, insulin, physical activity, epinephrine, insulin resistance, type 2 diabetes, glucose-6-phosphate, substrate affinity, enzyme kinetics, muscle glycogen, allosteric activation, UDP-glucose
MeSH terms
Allosteric Regulation, Animals, Diabetes Mellitus, Type 2, Epinephrine, Glycogen, Glycogen Synthase, Humans, Insulin, Insulin Resistance, Phosphorylation, Uridine Diphosphate Glucose, Exercise, Muscle, Skeletal

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