Grant: Operating Grant

Diabetes mellitus is rising in prevalence worldwide. The development of polyneuropathy, or damage to nerves, is a challenging complication of diabetes, noted in up to 50% of persons with diabetes mellitus. This condition, currently irreversible, results in loss of sensation, pain and increases the risk of lower limb amputation in patients. Our lab works on experimental models of diabetic polyneuropathy in mice and rats to understand how this condition develops and how it might be reversed. In this grant, we build on exciting findings that insulin, acting directly on neurons can encourage them to regrow and repair themselves from diabetic damage. This effect of insulin does not depend on blood glucose levels and in part involves a novel form of direct delivery to insulin receptors within the nervous system: intranasal insulin administration. We propose to enhance insulin's benefits by adding insulin sensitizing agents, by combining insulin with newly discovered insulin-related peptides, by removing barriers to insulin actions on neurons (reversing insulin 'resistance') and by discovering how diabetes and insulin alter gene function in nerve cells. Our goal is to identify how these approaches might lead to effective treatment of polyneuropathy in humans.