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Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment.
- Source :
- Diabetes; Apr2010, Vol. 59 Issue 4, p1082-1091, 10p, 2 Charts, 6 Graphs
- Publication Year :
- 2010
-
Abstract
- 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- to- 22-week streptozotocin (STZ)-induced 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 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 I diabetic rats is associated with impaired rates of respiratory activity and occurs without a significant rise in perikaryal ROS. Diabetes 59:1082-1091, 2010 [ABSTRACT FROM AUTHOR]
- Subjects :
- MITOCHONDRIAL pathology
GANGLIA
STREPTOZOTOCIN
PEOPLE with diabetes
INSULIN therapy
Subjects
Details
- Language :
- English
- ISSN :
- 00121797
- Volume :
- 59
- Issue :
- 4
- Database :
- Complementary Index
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 49834868
- Full Text :
- https://doi.org/10.2337/db09-1299