Diabetes is one of the leading causes of kidney disease, affecting approximately 30% of individuals with diabetes. Diabetic kidney disease (DKD) ultimately quadruples the risk of cardiovascular disease and mortality. Diabetes is characterised by a fundamental breakdown in glucose homeostasis. It has been observed that diabetes leads to an over-accumulation of the energy storage molecule glycogen (a highly branched polymer of glucose) in kidney tissue. This study was designed to characterise the molecular structure of this glycogen in order to gain insight into its molecular properties, allowing us to better predict possible effects it has on kidney health and blood glucose control.
Sprague-Dawley rats were given a single dose of Streptozotocin (STZ) (30 mg/kg) or a vehicle control at 4 weeks of age (N = 8) and were killed after the age of 16 weeks. The amount and structural parameters of kidney glycogen from the diabetic and control rats were analysed.
There were large accumulations of glycogen in the kidneys of rats with STZ induced diabetes, with very low amounts detected in the non-diabetic control animals. The structural parameters of the glycogen closely resemble muscle glycogen, consisting of the smaller b particles, contrasting with liver and heart glycogen which contains the much large a particles (which are many b particles attached together). The chain length distribution of these glycogen particles was also consistent with muscle glycogen, providing evidence that while the glycogen accumulates to abnormal levels, it does not resemble the longer-chained glycogen present in numerous glycogen storage diseases such as Lafora disease.
Understanding whether the glycogen that abnormally accumulates is protective (hero), pathological (villain) or inconsequential (bystander) will help determine whether there are therapeutic targets that mitigate diabetic kidney disease.