Diabetic peripheral neuropathy - Evidence for apoptosis and associated mitochondrial dysfunction

We hypothesized that diabetic sensory neuropathy is associated with activat ion of apoptosis and concomitant mitochondrial dysfunction. Studies were pe rformed in excised intact and acutely dissociated dorsal root ganglion (DRG ) neurons from control and streptozotocin-induced diabetic rats with decrea sed peripheral nerve conduction velocities (NCV). Apoptosis was increased i n acutely dissociated DRG neurons from 3- to 6-week-old diabetic rats. Basa l mitochondrial membrane potential (Delta psi) was significantly more posit ive in DRG neurons from diabetic rats. Depolarization with glutamate result ed in significantly more positive Delta psi and delayed recovery of Delta p si in neurons from diabetic rats. Restoration of euglycemia for 2 weeks wit h insulin implants normalized NCV, Delta psi, and apoptosis, Intact and acu tely dissociated neurons from diabetic rats demonstrated decreased Bcl-2 le vels and translocation of cytochrome C from the mitochondria to the cytopla sm. Neither levels of Bar nor levels of Bcl-X-L were altered in diabetic ne uropathy. Apoptosis associated with mitochondrial dysfunction may contribut e to the pathogenesis of diabetic sensory neuropathy.