Loading ...Objective.
Impairments in mitochondrial physiology may play a role in diabetic sensory neuropathy. We tested the hypothesis that mitochondrial dysfunction in sensory neurons is due to abnormal mitochondrial respiratory function.
Research Design And Methods.
Rates of oxygen consumption were measured in mitochondria from dorsal root ganglia (DRG) of 12-22 weeks streptozotocin (STZ)-diabetic rats, diabetic rats treated with insulin and age-matched controls. Activities and expression of components of mitochondrial complexes and reactive oxygen species (ROS) were analyzed.
Results.
Rates of coupled respiration with pyruvate + malate (P + M) and with ascorbate + TMPD (Asc + TMPD) in DRG were unchanged after 12 weeks diabetes. By 22 weeks of diabetes, respiration with P + M was significantly decreased by 31-44% and with Asc + TMPD by 29-39% compared to control. Attenuated mitochondrial respiratory activity of STZ-diabetic rats was significantly improved by insulin that did not correct other indices of diabetes. Activities of mitochondrial complexes I and IV and the Krebs cycle enzyme, citrate synthase, were decreased in mitochondria from DRG of 22 weeks STZ-diabetic rats compared to control. ROS levels in perikarya of DRG neurons were not altered by diabetes but ROS generation from mitochondria treated with antimycin A was diminished compared to control. Reduced mitochondrial respiratory function was associated with down-regulation of expression of mitochondrial proteins.
Conclusions.
Mitochondrial dysfunction in sensory neurons from type 1 diabetic rats is associated with impaired rates of respiratory activity and occurs without a significant rise in perikaryal ROS.
