Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Changes in glycogen structure over feeding cycle sheds new light on blood-glucose control (#240)

Mitchell A Sullivan 1 2 , Samuel T N Aroney 1 , Shihan Li 1 , Frederick J Warren 1 , Jin S Joo 3 , Ka Sin S Mak 4 , David I Stapleton 5 , Kim S Bell-Anderson 3 , Robert G Gilbert 1 2
  1. University of Queensland, St Lucia, QLD, Australia
  2. Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, Hubei, China
  3. School of Molecular Bioscience, Sydney, NSW, Australia
  4. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Kensington, New South Wales, Australia
  5. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC, Australia

Liver glycogen, a highly branched glucose polymer, has a critical role in the maintenance of blood glucose homeostasis. Liver glycogen has three levels of structure: 1) glucose units are attached to form linear chains via alpha-(1→4) linkages; 2) these chains are joined together via alpha-(1→6)-linked branch points to form highly branched glycogen “beta” particles (~20 nm in diameter); and 3) these beta particles are able to be joined together to form much larger “alpha” particles (~100-200 nm). Given the characteristically poor blood-glucose control associated with type 2 diabetes, a link between the structure/function relationships of liver-glycogen and type 2 diabetes is probable.  It has been shown that diabetic (db/db) mice have an impaired ability to synthesize the large composite glycogen a particles present in normal, healthy mice [1]. Recently, the structure of healthy mouse-liver glycogen over the diurnal cycle was characterised using size exclusion chromatography and transmission electron microscopy. Glycogen was observed to be initially formed as smaller beta particles, only being assembled into the larger alpha particles significantly after the time when glycogen content had reached a maximum [2]. This pathway, impaired in diabetic animals, is likely to give optimal blood-glucose control, as explained by the particles’ surface area to volume ratio. Lack of this control may result from, or contribute to, diabetes. This discovery suggests novel approaches to diabetes management.

  1. Sullivan, M. A., et al. (2011). "Molecular structural differences between type-2-diabetic and healthy glycogen." Biomacromolecules 12(6): 1983-1986.
  2. Sullivan, M. A., et al. (2014). "Changes in glycogen structure over feeding cycle sheds new light on blood-glucose control." Biomacromolecules 15(2): 660-665.