Diabetic Kidney Disease: Pathophysiology and Therapeutic Targets

Figure 2

(a) Glycolysis is the biochemical pathway in which glucose is broken down by cells to make energy. In a normoglycemic environment, that is, in patients without diabetes, glycolysis proceeds down its well described path without shunting into the polyol pathway, hexosamine pathway, or pathways that would lead to AGE production or PKC activation. (b) In a hyperglycemic environment, as would be seen in patients with either type 1 or type 2 diabetes, high glucose conditions lead to activation of excess superoxide which then inhibits the enzyme GADPH. This prevents glycolysis from proceeding down its natural course and creates a backlog of glycolysis precursors. Increased levels of glucose upregulate the polyol pathway whereas increased levels of fructose-6-phosphate upregulate the hexosamine pathway. Increased levels of glyceraldehyde-3-phosphate upregulate both AGE precursors and DAG, the latter being a cofactor for PKC activation.

(a)

(b)