Glucose and glycogen in the diabetic kidney: Heroes or villains?

Glucose metabolism in the kidney is currently foremost in the minds of nephrologists, diabetologists and researchers globally, as a result of the outstanding success of SGLT2 inhibitors in reducing renal and cardiovascular disease in individuals with diabetes. However, these exciting data have come with the puzzling but fascinating paradigm that many of the beneficial effects on the kidney and cardiovascular system seem to be independent of the systemic glucose lowering actions of these agents. This manuscript places into context an area of research highly relevant to renal glucose metabolism, that of glycogen accumulation and metabolism in the diabetic kidney. Whether the glycogen that abnormally accumulates is pathological (the villain), is somehow protective (the hero) or is inconsequential (the bystander) is a research question that may provide insight into the link between diabetes and diabetic kidney disease.