Diabetes and failure of axon regeneration in peripheral neurons

Peripheral neurons are targeted by a 'double hit' during diabetes mellitus. First, they are damaged directly; diabetic polyneuropathy is a progressive neurodegenerative disorder that involves sensory, autonomic and eventually motor neurons. The second 'hit' involves a profound impairment in the ability of peripheral axons to regenerate. This is important because the impairment impacts on how patients may recover from polyneuropathy. Moreover, diabetic patients also develop direct focal injures of peripheral nerves, such as carpal tunnel syndrome and ulnar neuropathy at the elbow. Their response to the treatment of these selective injuries is also impaired. Regeneration of peripheral neurons is normally a complex process that involves axon sprouting, upregulation of molecular regeneration programs, clearance of pathways for axon regrowth, maturation of new axons and reconnection to their targets. Schwann cells and perineuronal glial cells provide support during many of these processes. However, in diabetes mellitus a number of these steps may be independently impaired. In this brief article, we discuss evidence for several of these mechanisms of regenerative failure in diabetes.