Grant: Project Grant

Over half of all persons with diabetes mellitus, either type 1 or 2, develop polyneuropathy, or nerve damage. This entails loss of sensation in their skin, first in the feet then other areas of the body. Polyneuropathy develops because of progressive damage to sensory neurons that supply this sensation. Not only is there loss of sensation but also pain, with loss of balance and failure to recognize injury. Diabetic polyneuropathy predisposes people toward skin ulceration and amputation. There is no proven treatment in humans to arrest or reverse this chronic damage. The Zochodne laboratory is working on new ways to rescue sensory neurons from degeneration. This involves understanding why neuron branches, or axons for example in the skin, degenerate and disappear and fail to regenerate. These events may, surprisingly, also involve insulin, an action unrelated to its glucose lowering role. Here the Zochodne laboratory proposes to study and manipulate molecules that determine if axons can be rescued and regenerated in diabetes. The work involves finding molecules that support neurons from diabetic mice (culture studies) and applying these possible treatments to mice with experimental diabetes, including long term chronic disease, who show neuropathy similar to that experienced by humans. Preliminary work in the laboratory indicates that new approaches including insulin itself, or sensitizing its receptors so that it can be more effective, can slow degeneration and prompt regeneration of axons.These actions of insulin do not depend on its blood glucose lowering role. The laboratory plans to analyze how insulin supports nerves and how related and newer molecules may help.