Diabetes and the plasticity of sensory neurons

Diabetes mellitus targets sensory neurons during the development of peripheral neuropathy. While polyneuropathy is often routinely considered as another ‘microvascular’ complication of diabetes mellitus, this concept may no longer address the complexities and unique qualities of direct neuronal involvement. The list of altered molecules and pathways in diabetic neurons continues to grow and includes those related to structure, neuronal ‘stress’, and protection. A role for abnormal direct neuronal insulin signaling has emerged as an important contributing factor in neurodegeneration. Finally, important molecular players that influence neuronal and axon growth, such as PTEN (phosphatase and tensin homolog deleted on chromosome 10) are considered. A better mechanistic understanding of the pathogenesis of diabetic polyneuropathy may foster targeted therapies that reverse a long history of therapeutic failures.