The Controversial Role of Glucose in the Diabetic Kidney

The kidneys play an important role in maintaining glucose homeostasis being the main mechanisms, the gluconeogenesis, renal glucose consumption and glucose reabsorption in the proximal tubules. In this review, we present the main research into the role of glycogen-the stored form of glucose, and how it accumulates in the cells, providing new information on the link between diabetes and diabetic kidney disease. In the last 10 years, research under the scope of renal insulin handling, glucose transport in the proximal tubules, renal gluconeogenesis and renal insulin resistance, made possible to relate the roles of glucose and glycogen in the kidney with other several organs, like the liver. On the one hand, insulin positively regulates kidney uptake and degradation, and there is probably a specific action and resistance to insulin at the renal site. Moreover, insulin regulates the bioavailability of the sodium-glucose co-transporters-SGLT2 inhibitor, and inhibits renal gluconeogenesis. Only the liver and kidneys can supply glucose to the circulation through the process of gluconeogenesis, which involves the synthesis of glucose again from non-glycemic substrates; and the decomposition of stored glycogen. In the mind of nephrologists, diabetologists and scientists, glucose metabolism in the kidney is the focus, with the relevant success of inhibitors in reducing kidney and cardiovascular diseases in individuals with diabetes. However, these new data led to the intriguing paradigm that many of the beneficial effects on the renal and cardiovascular system appear to be independent of the systemic glucose-lowering actions of these agents. The goal of this work puts in context a highly relevant research area for renal glucose metabolism, of glycogen accumulation and metabolism in the diabetic kidney.