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

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.

Glycogen as a Building Block for Advanced Biological Materials

“…Drochmans and Orpin et al reported electron microscopy images and opalescence curves of rat liver and Moniezia expansa glycogen, respectively, in a range of solutions of increasing pH (from less than 2 up to 7.4). The studies confirmed the dissociation of the α‐particles into β‐particles at acidic pH, which is consistent with recent dynamic light scattering data …”

“…For some glycogen sources, typically the liver and heart, there is a third level of structure where these β‐particles are covalently joined into supramolecular complex particles called α‐particles (Figure A). These α‐particles hint at a tissue‐specific structure–function relationship as α‐ and β‐particles are enzymatically degraded to release glucose at different rates . Transmission electron microscopy (TEM) of glycogen particles from different sources demonstrates significant morphological differences in the structure of glycogen (Figure B–E).…”

“…Transmission electron microscopy (TEM) of glycogen particles from different sources demonstrates significant morphological differences in the structure of glycogen (Figure B–E). The β‐particle units are typically 20–50 nm in diameter, whereas the larger supramolecular α‐particles are polydisperse with a mean diameter of ≈150 nm accompanied with the smaller disperse β‐particles . Drochmans and Orpin et al reported electron microscopy images and opalescence curves of rat liver and Moniezia expansa glycogen, respectively, in a range of solutions of increasing pH (from less than 2 up to 7.4).…”

“…The most common schematic structure of glycogen is drawn as a regular tree‐ or dendrimer‐like structure that contains tiers of glucose chains, or branches, ordered into a self‐similar, or fractal structure . However, recent small‐angle X‐ray scattering data of glycogen β‐particles have allowed the application of robust polymer branching models that describe the evolution of branching as a function of particle radius. This has shown that glycogen β‐particles are best described as randomly hyperbranched polymer particles, rather than fractal structures, with a radius of gyration that scales with the logarithm of the molecular weight (i.e., R g ≈ log M ) .…”

Trifolium pratense (Red Clover) Improve SIRT1 Expression and Glycogen Content in High Fat Diet‐Streptozotocin Induced Type 2 Diabetes in Rats

“…Glycogen is an important glucose polymer which plays a vital role in glucose homeostasis . It has been well documented that insulin resistance, increased level of triglycerides and other lipids and accumulation of fat in liver are responsible for reduction in hepatic glycogen synthesis in type 2 diabetes .…”