Diabetic polyneuropathy (DPN) is a common but intractable degenerative disorder of peripheral neurons. DPN first results in retraction and loss of sensory terminals in target organs such as the skin, whereas the perikarya (cell bodies) of neurons are relatively preserved. This is important because it implies that regrowth of distal terminals, rather than neuron replacement or rescue, may be useful clinically. Although a number of neuronal molecular abnormalities have been examined in experimental DPN, several are prominent: loss of structural proteins, neuropeptides, and neurotrophic receptors; upregulation of "stress" and "repair" proteins; elevated nitric oxide synthesis; increased AGE-RAGE signaling, NF-κB and PKC; altered neuron survival pathways; changes of pain-related ion channel investment. There is also a role for abnormalities of direct signaling of neurons by insulin, an important trophic factor for neurons that express its receptors. While evidence implicating each of these pathways has emerged, how they link together and result in neuronal degeneration remains unclear. However, several offer interesting new avenues for more definitive therapy of this condition.
Keywords: diabetic polyneuropathy; dorsal root ganglia; insulin; sensory neurons.