Prolonged hyperglycemia is the critical etiological factor in the development of the microvascular complications of diabetes including diabetic nephropathy (1–2). The tissues subject to these complications appear to be susceptible by virtue of abundant expression of cell surface facilitative glucose transporters resulting in the transport of glucose down its concentration gradient. The fact that increased glucose uptake and metabolism promotes the pathological changes leading to tissue damage has led to great interest in the pathways of disposition of glucose metabolites and their regulation. There are at least five pathways of glucose metabolism that, either directly or indirectly, appear to contribute to the complications of diabetes. This current concept, reviewed by Brownlee (4), is supported by a number of studies. The increased cellular entry of glucose results first in augmented glycolytic flux and glucose oxidation. A byproduct of mitochondrial substrate metabolism, i.e., electron transport and oxidative phosphorylation, is superoxide, O₂-. The increased reactive oxygen species (ROS) production by mitochondria produces oxidative stress, a state in which the formation of ROS exceeds the capacity of cellular endogenous antioxidant removal systems. The excess ROS results in inhibition of the redox-sensitive glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), possibly via activation of poly-ADP-ribose polymerase (5). Poly-ADP-ribose polymerase activation is thought to be owing to ROS-induced DNA damage.