In this model, we propose that diabetes and peripheral neuropathy are the result of dysregulated TTX-S sodium channels, particularly TTX-S NaV1.3 and NaV1.7; both diabetes and painful neuropathy might occur as a result of NaV1.3 and/or NaV1.7 mutations or dysfunction, which increase vulnerability to injury in both small nerve fibers and pancreatic α and β cells. This evidence concerns the gene SCN3A and peripheral neuropathy.