5 minute lightning oral presentation (and poster) ESA-SRB 2023 in conjunction with ENSA

Exploring the fragility of liver glycogen alpha particles in diabetes (#213)

Ziyi Wang 1 , Mitchell Sullivan 2 , Liang Wang 1 3 , Robert Gilbert 4 5
  1. Queensland Alliance for Agriculture and Food Innovation, University of Queensland, Saint Lucia, QLD, Australia
  2. Glycation and Diabetes, Mater Research Institute, The University of Queensland-Translational Research Institute, Brisbane, QLD, Australia
  3. Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong, China
  4. Key Laboratory of Plant Functional Genomics of the Ministry of Education/Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding, College of Agriculture, Yangzhou University, Yangzhou, Jiangsu, China
  5. Co-Innovation Center for Modern Production Technology of Grain Crops, Yangzhou University, Yangzhou, Jiangsu, China

Aims:The formation mechanism of glycogen α particles, derived from smaller β particles, remains elusive. In wild-type mice during glycogen synthesis (active state), extracted liver glycogen is vulnerable to DMSO-induced degradation into β particles [1]. Conversely, glycogen particles remain stable during glycogen breakdown (resting state) [1]. However, diabetic mice exhibit fragile liver glycogen in both synthesis and breakdown phases [2]. This α particle fragility could be common among diabetic mammals, linked to features like hyperglycemia. Prior research has mainly focused on diabetic mice, limiting human relevance. Our primary goal was to probe hepatic glycogen fragility susceptibility in individuals with and without diabetes, illuminating potential universality among diabetic mammals. Additionally, we aimed to identify proteins within the livers of diabetic and non-diabetic mice and humans, which might contribute to α glycogen particle vulnerability.
Methods:We employed diabetic and non-diabetic mice, alongside human liver tissues, as experimental materials. Fluorophore-assisted carbohydrate electrophoresis, size-exclusion chromatography, and transmission electron microscopy revealed structural glycogen features. Proteomics analysis explored differential protein expression in liver tissues of diabetic and non-diabetic subjects.
Results:Diabetic mice and humans displayed significantly larger average glycogen chain lengths during glycogen breakdown, compared to non-diabetic counterparts. Both groups exhibited liver glycogen fragility after DMSO treatment [3]. Seven overlapping proteins emerged between differential expression proteins in diabetic and non-diabetic liver tissues. Notably, the glycogen-associated protein PPP1R3G was significantly downregulated in diabetics, consistent with diurnal healthy mouse protein expression patterns. Specifically, PPP1R3G upregulation during glycogen breakdown implied stable α glycogen, while its downregulation during synthesis suggested fragile α glycogen dominance.
Conclusion:Liver glycogen is more fragile in diabetic individuals, indicating widespread fragility of α glycogen among diabetic mammals. The PPP1R3G protein may contribute to α glycogen structure fragility.

  1. [1] WANG, M., LIU, Q., LI, F., TANG, J., XIONG, X., YANG, Y., JU, P., WANG, Z., GILBERT, R. G. & WANG, L. 2021. The dynamic changes of glycogen molecular structure in Escherichia coli BL21(DE3). Carbohydrate Polymers, 259, 117773
  2. [2] HU, Z., DENG, B., TAN, X., GAN, H., LI, C., NADA, S. S., SULLIVAN, M. A., LI, J., JIANG, X., LI, E. & GILBERT, R. G. 2018. Diurnal changes of glycogen molecular structure in healthy and diabetic mice. Carbohydrate Polymers, 185, 145-52.
  3. [3] WANG, Z., MIN, X., HU, Z., SULLIVAN, M. A., TANG, Y., WANG, L., GILBERT, R. G., SHI, C. & DENG, B. 2022. The fragility of liver glycogen from humans with type 2 diabetes: A pilot study. International Journal of Biological Macromolecules, 221, 83-90.