Intranasal insulin modulates hippocampal amyloid ß (Aß) levels by regulating glycogen synthase kinase (GSK)-3a in diabetic rats.

Diabetes and Alzheimer disease (AD), two age related diseases, are on the rise across the globe. Recent studies have demonstrated diabetes as a major risk factor for AD. Disturbances in insulin signaling pathway appear to be the connecting link between the two illnesses. In the present study, we characterized a non-transgenic streptozotocin induced type 1 diabetic rat model and the effect of treatment with insulin. Five weeks of insulin deficient diabetes significantly reduced the insulin degrading enzyme activity and increased glycogen synthase kinase (GSK)-3a levels. Treatment with insulin resulted in suppression of GSK-3a levels, one of the major modulators of Aß synthesis. These findings strengthen intranasal insulin treatment as a therapeutic modality in reducing the AD-like features in the brain. [ABSTRACT FROM AUTHOR]