Molecular-size dependence of glycogen enzymatic degradation and its importance for diabetes

Abstract

Glycogen, a hyperbranched glucose polymer, is the blood-sugar reservoir in animals. Liver glycogen comprises small β particles, which can join together as large composite α particles. It had been shown that the binding between β in α particles in the liver of diabetic mice is more fragile than in healthy mice. This could be linked to the loss of blood-sugar control characteristic of diabetes if the rate per monomer unit of the enzymatic degradation to glucose of α particles were significantly slower than that of β particles. This is tested here by examining the in vitro time evolution of the molecular size distribution of glycogen from the livers of healthy and diabetic mice and rats, containing distinct components of both α and β particles; this treatment is analogous to the “competitive growth” method used to explore mechanisms in emulsion polymerization. Simulations for the time evolution of the molecular size distribution were also performed. It is found that the degradation rate per monomer unit is indeed faster for the smaller particles, supporting the hypothesis of a causal link between chemical fragility of glycogen from diabetic liver with poor control of blood-sugar release. Comparison between simulations and experiment indicate that α and β particles have significant structural differences.