Abstract
Glycogen is a highly-branched polysaccharide that is widely distributed across the three life domains. It has versatile functions in physiological activities such as energy reserve, osmotic regulation, blood glucose homeostasis, and pH maintenance. Recent research also confirms that glycogen plays important roles in longevity and cognition. Intrinsically, glycogen function is determined by its structure that has been intensively studied for many years. The recent association of glycogen α-particle fragility with diabetic conditions further strengthens the importance of glycogen structure in its function. By using improved glycogen extraction procedures and a series of advanced analytical techniques, the fine molecular structure of glycogen particles in human beings and several model organisms such as Escherichia coli, Caenorhabditis elegans, Mus musculus, and Rat rattus have been characterized. However, there are still many unknowns about the assembly mechanisms of glycogen particles, the dynamic changes of glycogen structures, and the composition of glycogen associated proteins (glycogen proteome). In this review, we explored the recent progresses in glycogen studies with a focus on the structure of glycogen particles, which may not only provide insights into glycogen functions, but also facilitate the discovery of novel drug targets for the treatment of diabetes mellitus.
Highlights
By using E. coli BL21(DE3) as a model organism, we recently revealed that glycogen α particles in bacteria followed a similar pattern of structural change as in healthy liver, that is, fragile during synthesis stage and stable during degradation stage (Wang M. et al, 2021); in addition, fragile glycogen particles tend to have longer chain length distribution than stable glycogen particles (Wang M. et al, 2021), which is consistent with previous results in healthy and diabetic mice (Hu et al, 2018)
Delicate studies revealed that fragility of glycogen α particles was associated with the development of diabetes in animal models, which suggested that novel drug targets might exist for diabetic treatment, the possibility of developing novel anti-diabetic drugs
Uncovering the mechanisms of glycogen α-particle assembly and fragility in prokaryotes like E. coli and lower life forms such as C. elegans could be able to help us understand the similar processes in animals and human beings
Summary
Glycogen is a highly branched polysaccharide that is widely distributed across species from prokaryotes to eukaryotes (Wilson et al, 2010), which plays pivotal roles in a variety of extremely important functions, such as energy reserve (Greenberg et al, 2006), osmotic pressure maintenance (Brown, 2004), host colonization (Jones et al, 2008), blood glucose homeostasis (Han et al, 2016), pH maintenance (Fredricks et al, 2014) and tumor development (Zhang et al, 2020). The structure of liver glycogen α particles has been reported to be associated with the development of type 2 diabetes (Sullivan et al, 2012; Besford et al, 2015; Deng et al, 2015). Since C. elegans is often used to study diabetes, it would be convenient to use the model animal to elucidate the assembly mechanisms of glycogen structure (Hanover et al, 2005; Zhu et al, 2016). Morphological studies of glycogen particles from Selenomonas ruminantium and Fibrobacter succinogenes via transmission electron microscopy (TEM) showed the possible existence of rosette-shaped α particles in bacteria, though no much attention was given to the discovery (Kamio et al, 1981; Gong and Forsberg, 1993). Insights from this review would facilitate our understanding of glycogen structural fragility, with potentials in developing novel drug targets for the treatment of diabetes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
