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Liver glycogen in type 2 diabetic mice is randomly branched as enlarged aggregates with blunted glucose release

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Abstract

Glycogen is a vital highly branched polymer of glucose that is essential for blood glucose homeostasis. In this article, the structure of liver glycogen from mice is investigated with respect to size distributions, degradation kinetics, and branching structure, complemented by a comparison of normal and diabetic liver glycogen. This is done to screen for differences that may result from disease. Glycogen α-particle (diameter ∼ 150 nm) and β-particle (diameter ∼ 25 nm) size distributions are reported, along with in vitro γ-amylase degradation experiments, and a small angle X-ray scattering analysis of mouse β-particles. Type 2 diabetic liver glycogen upon extraction was found to be present as large loosely bound, aggregates, not present in normal livers. Liver glycogen was found to aggregate in vitro over a period of 20 h, and particle size is shown to be related to rate of glucose release, allowing a structure-function relationship to be inferred for the tissue specific distribution of particle types. Application of branching theories to small angle X-ray scattering data for mouse β-particles revealed these particles to be randomly branched polymers, not fractal polymers. Together, this article shows that type 2 diabetic liver glycogen is present as large aggregates in mice, which may contribute to the inflexibility of interconversion between glucose and glycogen in type 2 diabetes, and further that glycogen particles are randomly branched with a size that is related to the rate of glucose release.

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Acknowledgments

The assistance from Dr. Nigel Kirby and Nathan Cowieson at the SAXS beamline is gratefully acknowledged. QAB and XYZ would like to thank the Australian government for APA scholarships, and the Univeristy of Melbourne for receipt of the Albert Shimmins award and the Norma Hilda Schuster scholarship (QAB). This study was partially supported by funding from the Melbourne Materials Institute (QAB, AGW), the Australian Synchrotron (beamline time) (QAB, AGW), the Victorian Life Sciences Computation Initiative (QAB, AGW, Grant No. VRO252), and the Australian Research Council for grant ARCDP110102396 (JMY).

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Correspondence to Quinn Alexander Besford.

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Besford, Q.A., Zeng, XY., Ye, JM. et al. Liver glycogen in type 2 diabetic mice is randomly branched as enlarged aggregates with blunted glucose release. Glycoconj J 33, 41–51 (2016). https://doi.org/10.1007/s10719-015-9631-5

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