Liver glycogen is a highly branched polymer of glucose important for the maintenance of blood-glucose levels. Liver glycogen contains composite α particles (up to ~300 nm in diameter), made up of small linked β particles (~20 nm in diameter). A past study using dimethyl sulfoxide size exclusion chromatography observed that diabetic (db/db) mice had fewer of the large α particles found in the hepatocytes of healthy mice.¹ Here, using an aqueous size exclusion chromatography system² we show that db/db mice have a relative quantity of large liver glycogen α particles comparable to that of the healthy controls. We show that while these diabetic mice have a similar quantity of α particles, these particles fall apart in dimethyl sulfoxide, with the α particles from the healthy controls being resistant to this degradation.(see Fig.1) This explains why the past study utilizing dimethyl sulfoxide size exclusion chromatography observed fewer α particles in the diabetic mice. The difference in stability of liver glycogen α particles in diabetic and healthy mice may give important clues into differences between the structure of the glycogen and its ability to act as a blood-glucose buffer. If this more fragile liver glycogen is resulting in a sub-optimal regulation of blood glucose then this discovery could be an important step in determining treatment methods that alleviate the effects of type 2 diabetes.

Fig.1 SEC weight distribution w(log R_h), where R_h is a molecular size (the hydrodynamic radius), of A) healthy glycogen samples (untreated, blue; treated with DMSO, yellow) and B) diabetic glycogen samples (untreated glycogen, red; treated with DMSO, yellow). All distributions are normalized to equal maxima.