Glucose loading induces DNA fragmentation in rat proximal tubular cells

A 10% glucose, 10% mannitol, or 0.9% saline solution was infused in male Wistar rats for 300 minutes via the left cervical vein. Glomerular filtration rates (GFRs) were not significantly altered in any of the three groups. DNA was extracted from isolated proximal tubular cells at the end of each infusion. Electrophoresis on agarose gels showed a distinct ladder pattern of DNA fragmentation in 10% glucose-loaded rats, but no such pattern in 10% mannitol- or 0.9% saline-loaded rats. After infusion for 300 minutes, the plasma glucose level of the 10% glucose-loaded group was higher than that of the other two groups (each P < .005). These results suggest that hyperglycemia led to DNA fragmentation in the DNA of proximal tubular cells, similar to the process of programmed cell death known as apoptosis. DNA fragmentation may be associated with renal proximal tubular damage in the early stages of diabetic nephropathy.