Insulin prevents aberrant mitochondrial phenotype in sensory neurons of type 1 diabetic rats

Diabetic neuropathy affects approximately 50% of diabetic patients. Down-regulation of mitochondrial gene expression and function has been reported in both human tissues and in dorsal root ganglia (DRG) from animal models of type 1 and type 2 diabetes. We hypothesized that loss of direct insulin sig...

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Bibliographic Details
Published in:Experimental neurology 2017-11, Vol.297, p.148-157
Main Authors: Aghanoori, Mohamad-Reza, Smith, Darrell R., Roy Chowdhury, Subir, Sabbir, Mohammad Golam, Calcutt, Nigel A., Fernyhough, Paul
Format: Article
Language:English
Subjects:
Animals
Axon regeneration
Bioenergetics
Cells, Cultured
Diabetes Mellitus, Experimental - metabolism
Diabetes Mellitus, Experimental - prevention & control
Diabetes Mellitus, Type 1 - metabolism
Diabetes Mellitus, Type 1 - prevention & control
Diabetic neuropathy
Dorsal root ganglia
Insulin - pharmacology
Insulin - therapeutic use
Male
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondrial function
Neurotrophin
Phenotype
Rats
Rats, Sprague-Dawley
Sensory Receptor Cells - metabolism
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Summary:Diabetic neuropathy affects approximately 50% of diabetic patients. Down-regulation of mitochondrial gene expression and function has been reported in both human tissues and in dorsal root ganglia (DRG) from animal models of type 1 and type 2 diabetes. We hypothesized that loss of direct insulin signaling in diabetes contributes to loss of mitochondrial function in DRG neurons and to development of neuropathy. Sensory neurons obtained from age-matched adult control or streptozotocin (STZ)-induced type 1 diabetic rats were cultured with or without insulin before determining mitochondrial respiration and expression of mitochondrial respiratory chain and insulin signaling-linked proteins. For in vivo studies age-matched control rats and diabetic rats with or without trace insulin supplementation were maintained for 5months before DRG were analyzed for respiratory chain gene expression and cytochrome c oxidase activity. Insulin (10nM) significantly (P
ISSN:0014-4886
1090-2430
DOI:10.1016/j.expneurol.2017.08.005