Dual-action peptides: a new strategy in the treatment of diabetes-associated neuropathy

Peripheral neuropathy is one of the most common and debilitating complications of type 1 and type 2 diabetes mellitus. Recent studies have shown that several small, non-neural peptides possess neurotrophic activity and exert beneficial effects on nervous system function in experimental and clinical diabetes. Two of these, C-peptide and islet neogenesis-associated protein peptide, are derived from pancreatic proteins and use related signal transduction mechanisms. Derivatives of erythropoietin possess similar properties in the nervous system. As a group, these peptides are of increasing interest as leads to potential new approaches in the treatment of diabetes-associated neuropathies and other neurodegenerative conditions. This review addresses the recent advances made with these peptides in the context of diabetic neuropathy, and highlights similarities and differences in their mechanisms of action from the perspective of combination therapy.