This study demonstrates that experimental alcohol-related peripheral neuropathy can develop in the absence of nutritional deficiencies, including thiamine, and is characterized by (1) slowed conduction velocity due to predominantly demyelination, although a small component of axonal degeneration co-exists; (2) peripheral nerve insulin and IGF resistance, which occurs at multiple levels in the cascades, including at the insulin/IGF receptors, similar to the effects of ethanol on liver and brain; and (3) degeneration of myelin and axonal cytoskeletal proteins. Here, INS is linked to peripheral neuropathy.