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Because of the first observation of apoptosis in the PNS less than a decade ago, the balance of evidence supports the concept that PCD occurs in cells of the PNS in the presence of diabetes, elevated glucose levels, or insulin deprivation. In general, measured apoptosis is more severe in DRG neurons than in autonomic neurons, or SC. Ultimately, DRG neuronal death is a balance between finely regulated but often opposing pathways. Evidence of PCD or organellar damage often exceeds the observed DRG neuronal loss. This raises the question, is DRG neuronal loss of significance in the pathogenesis of diabetic neuropathy? Apoptosis represents only the final pathological observation in this state of organellar failure or suboptimal organelle function. It is likely that even nonapoptotic neurons exhibit impaired metabolic function and protein synthesis and this dysregulation will in part induce neuropathy. More importantly, the primary precipitating events leading to apoptosis in the PNS need to be clearly delineated if it is to be understood how to intervene or prevent the most common complication of diabetes, namely neuropathy.

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