Role of Glucose Metabolism and Mitochondrial Function in Diabetic Kidney Disease

Diabetic kidney disease (DKD) continues to be the primary cause of chronic kidney disease in the USA and around the world. The numbers of people with DKD also continue to rise despite current treatments. Certain newer hypoglycemic drugs offer a promise of slowing progression, but it remains to be seen how effective these will be over time. Thus, continued exploration of the mechanisms underlying the development and progression of DKD is essential in order to discover new treatments. Hyperglycemia is the main cause of the cellular damage seen in DKD. But, exactly how hyperglycemia leads to the activation of processes that are ultimately deleterious is incompletely understood.

Studies primarily over the past 10 years have provided novel insights into the interplay of hyperglycemia, glucose metabolic pathways, mitochondrial function, and the potential importance of what has been called the Warburg effect on the development and progression of DKD. This review will provide a brief overview of glucose metabolism and the hypotheses concerning the pathogenesis of DKD and then discuss in more detail the supporting data that indicate a role for the interplay of glucose metabolic pathways and mitochondrial function.