Blood glucose control is a fundamental necessity for sustaining human life. Disruption of this intricate system, for example in diabetes which affects over 537 million individuals worldwide, can result in severe complications and increased mortality. A pivotal aspect of blood glucose regulation revolves around the storage of glucose in highly branched polymers known as glycogen, our “glucose batteries”. The indispensability of healthy glycogen is underscored by its ubiquitous presence in organisms ranging from bacteria to mammals, as well as its presence across a wide range of tissues and cell types in humans.
In most tissues, an individual glycogen particle, termed β particle, will reach sizes of ~50,000 glucose molecules (~30 nm in diameter). In the liver, these β particles, via a currently unknown mechanism, form agglomerates known as α particles (~100-200 nm in diameter).
The following insights into the interplay between glycogen and diabetes have emerged: 1) Liver glycogen α particles in diabetes are molecularly fragile and contain longer chain-lengths, potentially contributing to a failure in blood glucose homeostasis; 2) abnormally large levels of glycogen accumulates in the kidneys of individuals with diabetes, the consequence of which remains unknown. The pathological potential of abnormal aggregations of glycogen is made evidence by several severe and often fatal glycogen storage disease, for example Lafora Disease and Andersen’s Disease.
The discoveries regarding diabetes and glycogen structure/metabolism have sparked a number of ongoing investigations, including: 1) A search to discover what binds the smaller β particles together, to form large α particles in the liver; 2) investigations on whether common anti-diabetic drugs affect glycogen levels and structure; and 3) concerted efforts to determine the effect of abnormal kidney glycogen on kidney function and blood glucose homeostasis in preclinical models of diabetes.