The role of growth factors in diabetic peripheral neuropathy

Peripheral neuropathy afflicts 60% of all diabetic patients. Underlying the clinical disorder is the loss or degeneration of neurons, Schwann cells, and neuronal fibers. This degenerative pathology has prompted interest in the potential of growth factors as a therapy in diabetic neuropathy. Three lines of evidence support the theory that growth factors may be important in this disorder: (1) endogenous growth factors promote survival and health of neurons, (2) expression levels of growth factors are altered in diabetic neuropathy and peripheral neuron injury, and (3) growth factors induce neuronal regeneration in in vitro and in vivo models of diabetic injury. This review surveys the roles of several growth factors in diabetic neuropathy, including the neurotrophins, insulin-like growth factors, cytokine-like growth factors, and vascular endothelial growth factor. These growth factors are examined in terms of their expression during peripheral nerve injury and their protective and regenerative effects on peripheral neurons. Growth factor-mediated neuroprotective signaling is discussed, particularly in relation to the recent research, suggesting that diabetic neuropathy-induced degeneration stems from oxidative stress. Finally, the potential of growth factors as therapeutic agents is addressed, including an assessment of past growth factor clinical trials and other potential avenues of growth factor therapy.