In diabetic rat sensory neurons, reduced respiratory chain activity leads to diminished superoxide generation, indicating that alternative mechanisms like the polyol pathway drive oxidative stress under high glucose conditions.
Abnormal mitochondrial function correlated with a downregulation of mitochondrial proteins, with components of the respiratory chain targeted in lumbar DRG in diabetes. The reduced activity of the respiratory chain was associated with diminished superoxide generation within the mitochondrial matrix and did not contribute to oxidative stress in axons of diabetic neurons. Alternative pathways involving polyol pathway activity appear to contribute to raised ROS in axons of diabetic neurons under high glucose concentration.
Akude et al. (Tue,) studied this question.