Diurnal changes of glycogen molecular structure in healthy and diabetic mice

Is liver glycogen fragility a possible drug target for diabetes?

“…6 The results showed that only GN was robustly detected in all samples from rats, mice, and humans, suggesting that the GN protein was the binding glue among β particles. 16 This could explain the findings that more dense but fragile (in terms of in vitro DMSO treatment) glycogen α particles were formed in C57 db/db type 2 diabetic mice when compared to healthy C57 mice. Together with the abnormal CLD observed from in db/db mice, a possible mechanism could be put forward for the formation of fragile glycogen α particles; the glycogen β particles with longer chains and a lower branching degree have less steric hindrance for the GN diffusion, and therefore, more GN proteins are located within β particles instead of functioning as the binders among β particles ( Figure 6B).…”

“…The SEC weight distributions of glycogen from healthy mice do not show obvious changes before and after DMSO treatment, while the size distribution of glycogen molecules from diabetic mice changed significantly after DMSO treatment ( Figure 4B), that is, the α particles were molecularly fragile, although some α particles resisted DMSO treatment. 16 Studies that are ethically permitted have shown structural molecular similarities between liver glycogen from humans and mice. After DMSO treatment, only glycogen from diabetic mice had lower densities in the α particle region (R h ~ 40 nm), while wild-type glycogen particles shared similar densities.…”

“…[71][72][73][74] The liver glycogen content was found to reach a maximum at night and then drop to lower levels during the day (Figure 2). 70 A reinforcement process of the compact but fragile (toward in vitro DMSO degradation) glycogen α particles into loose but resistant α particles may occur during F I G U R E 4 A scheme showing the alteration of fragile/stable glycogen particles during in vitro DMSO treatment (A), and the corresponding changes of particle size distribution (B), and density distribution (C) before (blue curve) and after (red curve) DMSO treatment of fragile glycogen particles 16 F I G U R E 5 Schematic of structural changes of healthy C57BL/6J and diabetic db/db mouse liver glycogen over a diurnal cycle (A), and the feedback loop between high blood glucose levels and fragile α particles (B). 70 A reinforcement process of the compact but fragile (toward in vitro DMSO degradation) glycogen α particles into loose but resistant α particles may occur during F I G U R E 4 A scheme showing the alteration of fragile/stable glycogen particles during in vitro DMSO treatment (A), and the corresponding changes of particle size distribution (B), and density distribution (C) before (blue curve) and after (red curve) DMSO treatment of fragile glycogen particles 16 F I G U R E 5 Schematic of structural changes of healthy C57BL/6J and diabetic db/db mouse liver glycogen over a diurnal cycle (A), and the feedback loop between high blood glucose levels and fragile α particles (B).…”

“…70 A reinforcement process of the compact but fragile (toward in vitro DMSO degradation) glycogen α particles into loose but resistant α particles may occur during F I G U R E 4 A scheme showing the alteration of fragile/stable glycogen particles during in vitro DMSO treatment (A), and the corresponding changes of particle size distribution (B), and density distribution (C) before (blue curve) and after (red curve) DMSO treatment of fragile glycogen particles 16 F I G U R E 5 Schematic of structural changes of healthy C57BL/6J and diabetic db/db mouse liver glycogen over a diurnal cycle (A), and the feedback loop between high blood glucose levels and fragile α particles (B). 15,70 This in vitro fragility of α particles results in their degradation into smaller β particles, which can rapidly degrade into glucose as mentioned above. A reinforcement process of the compact but fragile (toward DMSO degradation) glycogen α particles into loose but resistant α particles is present in healthy mice during the dark-to-light transformation stage but not in type 2 db/db mice the dark-to-light transformation stage.…”

“…9 In many developed and developing countries, type 2 diabetes is reaching epidemic proportions. 15,16 Furthermore, it has been shown that the glycogen phosphorylase-catalyzed in vitro degradation of β particles occurs at a higher rate when compared to that of α particles, 17 thereby indicating that the glycogen fragility at least in part contributes to poor blood glucose regulation in diabetic mice. 14 Liver glycogen is involved in maintaining blood glucose homeostasis.…”