Context: Liver glycogen, a highly branched glucose polymer, helps maintain glucose homeostasis. It comprises α particles, which are composites of many smaller β particles bound together, plus a small amount of bound protein. In db/db mice, a model for type 2 diabetes, glycogen α particles have been found to be readily degraded into β particles by addition of a hydrogen-bond disruptor, DMSO (1). β particles enzymatically degrade more rapidly to glucose in vitro, consistent with diabetic hyperglycemia (2). Both a diet such that starch degradation is slow to release glucose during digestion, and traditional Chinese medicine (TCM), are commonly used to manage diabetes.
Methods: This research used db/db mice and studied the molecular structural difference between both diet-controlled and TCM-treated and untreated diabetic mouse-liver glycogen. Four TCM, astragalus polysaccharide (APS), berberine (BBR), panax notoginseng saponins (PNS) and pueraria flavonoid (PF), were used. To study the effects of controlled diets, mice were fed one of the following three diets: standard chow containing ordinary starch (control), or two chows which were the same as that for ordinary chow but where the starch was one of two slowly digested starches, Gelose 50 or Gelose 80. Glycogen fragility was tested with the addition of DMSO solution (hydrogen bond breaker), with molecular size distribution being measured by size-exclusion chromatography.
Findings: The blood glucose level and glycogen content of diabetic mice were significantly lowered after diet-controlled, APS, BBR and PF treatments. All methods showed that the liver glycogen in treated diabetic mice were no longer molecularly fragile to the H-bond disruptor. Thus all of these proven diabetes treatments avoided the molecular fragility that has been found to be characteristic for diabetic liver glycogen.
Innovative contribution to research: Understanding the mechanism of this fragility prevention may indicate novel drug targets for diabetes management.