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Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment

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...

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Autores principales: Chowdhury, Subir K. Roy, Zherebitskaya, Elena, Smith, Darrell R., Akude, Eli, Chattopadhyay, Sharmila, Jolivalt, Corinne G., Calcutt, Nigel A., Fernyhough, Paul
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844817/
https://www.ncbi.nlm.nih.gov/pubmed/20103706
http://dx.doi.org/10.2337/db09-1299
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author Chowdhury, Subir K. Roy
Zherebitskaya, Elena
Smith, Darrell R.
Akude, Eli
Chattopadhyay, Sharmila
Jolivalt, Corinne G.
Calcutt, Nigel A.
Fernyhough, Paul
author_facet Chowdhury, Subir K. Roy
Zherebitskaya, Elena
Smith, Darrell R.
Akude, Eli
Chattopadhyay, Sharmila
Jolivalt, Corinne G.
Calcutt, Nigel A.
Fernyhough, Paul
author_sort Chowdhury, Subir K. Roy
collection PubMed
description 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 1 diabetic rats is associated with impaired rates of respiratory activity and occurs without a significant rise in perikaryal ROS.
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spelling pubmed-28448172011-04-01 Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment Chowdhury, Subir K. Roy Zherebitskaya, Elena Smith, Darrell R. Akude, Eli Chattopadhyay, Sharmila Jolivalt, Corinne G. Calcutt, Nigel A. Fernyhough, Paul Diabetes Original Article 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 1 diabetic rats is associated with impaired rates of respiratory activity and occurs without a significant rise in perikaryal ROS. American Diabetes Association 2010-04 2010-01-26 /pmc/articles/PMC2844817/ /pubmed/20103706 http://dx.doi.org/10.2337/db09-1299 Text en © 2010 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Article
Chowdhury, Subir K. Roy
Zherebitskaya, Elena
Smith, Darrell R.
Akude, Eli
Chattopadhyay, Sharmila
Jolivalt, Corinne G.
Calcutt, Nigel A.
Fernyhough, Paul
Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment
title Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment
title_full Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment
title_fullStr Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment
title_full_unstemmed Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment
title_short Mitochondrial Respiratory Chain Dysfunction in Dorsal Root Ganglia of Streptozotocin-Induced Diabetic Rats and Its Correction by Insulin Treatment
title_sort mitochondrial respiratory chain dysfunction in dorsal root ganglia of streptozotocin-induced diabetic rats and its correction by insulin treatment
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844817/
https://www.ncbi.nlm.nih.gov/pubmed/20103706
http://dx.doi.org/10.2337/db09-1299
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