1. Mitochondrial respiratory chain dysfunction in dorsal root ganglia of streptozotocin-induced diabetic rats and its correction by insulin treatment
- Author
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Chowdhury, Subir K. Roy, Zherebitskaya, Elena, Smith, Darrell R., Akude, Eli, Chattopadhyay, Sharmila, Jolivalt, Corinne G., Calcutt, Nigel A., and Fernyhough, Paul
- Subjects
Type 1 diabetes -- Complications and side effects -- Research ,Insulin -- Health aspects -- Research ,Mitochondrial diseases -- Risk factors -- Care and treatment -- Complications and side effects -- Research ,Sensory receptors -- Health aspects -- Research ,Health - Abstract
OBJECTIVE--Impairments in mitochondrial physiology may play a role in diabetic sensory neuropathy. We tested the hypothesis that mitochondriai 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- to- 22-week streptozotocin (STZ)-induced diabetic rats, diabetic rats treated with insulin, and age-matched controls. Activities and expression of components of mitochondriai 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 of diabetes. By 22 weeks of diabetes, respiration with P + M was significantly decreased by 31-44% and with Asc + TMPD by 29-39% compared with 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-week STZ-diabetic rats compared with 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 with control. Reduced mitochondrial respiratory function was associated with downregulation 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., Peripheral nerves of diabetic patients develop a spectrum of pathology that can take many years to emerge (1,2). Experimental studies over shorter time periods have demonstrated that hyperglycemia can induce [...]
- Published
- 2010
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