Diurnal changes of glycogen molecular structure in healthy and diabetic mice

• Published in: Carbohydrate polymers 2018-04, Vol.185, p.145-152
• Main Authors: Hu, Zhenxia, Deng, Bin, Tan, Xinle, Gan, Hua, Li, Cheng, Nada, Sharif S., Sullivan, Mitchell A., Li, Jialun, Jiang, Xiaoyin, Li, Enpeng, Gilbert, Robert G.
• Format: Article
• Language: English
• Subjects: Characterization; Diabetes; Glycogen; GPC; Molecular structure
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2018.01.003

•Glycogen is complex branched glucose polymer, reservoir for blood sugar in animals.•Has multi-level structure, including bound aggregates of smaller glycogen molecules.•This binding is fragile in diabetic liver glycogen.•Data on fragility as a function of time after feeding suggests biosynthesis mechanism.•Molecular origin of fragility suggests it arises from glycogen biosynthesis enzymes. Glycogen is a complex branched glucose polymer functioning as a blood-sugar reservoir in animals. Liver glycogen β particles can bind together to form α particles, which have a slower enzymatic degradation to glucose. The linkage between β particles in α particles in diabetic liver breaks (is fragile) in dimethyl sulfoxide (DMSO), a H-bond disruptor, consistent with blood-sugar homeostasis loss in diabetes. We examined diurnal changes in the molecular structure of healthy and diabetic mouse-liver glycogen. Healthy mouse glycogen was fragile to DMSO during glycogen synthesis but not degradation; diabetic glycogen was always fragile. Two alternative mechanisms for this are suggested: healthy glycogen is fragile when formed and becomes stable during subsequent degradation, a process damaged in diabetes; alternatively, there are two types of glycogen: one compact but fragile and the other loose but non-fragile. This suggests potential types of diabetes drug targets through modifying the activities of glycogen synthesis enzymes.