Dorsal root ganglia (DRG) neurons degenerate in diabetic neuropathy (DN) and 
exhibit mitochondrial damage. We studied mitochondria of cultured DRG neurons 
exposed to high glucose as an in vitro model of DN. High glucose sequentially 
increases the expression, activation and localization of the pro-apoptotic 
proteins Bim and Bax and the mitochondrial fission protein dynamin-regulated 
protein 1 (Drp1). High glucose causes association of Drp1/Bax, similar to other 
apoptotic stimuli. Collectively, these events promote mitochondrial 
fragmentation and reduce mitochondrial number, suggestive of apoptotic 
mitochondrial fission. Drp1 is also upregulated in DRG from experimentally 
diabetic rats, suggesting a role for mitochondrial fission in DN. Insulin-like 
growth factor-I (IGF-I) protects high glucose-treated DRG neurons by preventing 
mitochondrial accumulation of Bim and Bax but does not modulate Drp1 expression 
or localization. We propose that mitochondria are compromised by convergence of 
Bim/Bax proteins with Drp1, which contributes to high glucose-induced injury in 
DRG neurons.