We have evaluated the effect of peripheral insulin deficiency on brain insulin pathway activity in a mouse model of type-1 diabetes, the parallels with Alzheimer’s disease (AD) and the effect of treatment with insulin.
Nine weeks of insulin-deficient diabetes significantly impaired the learning capacity of mice, significantly reduced IDE protein expression and significantly reduced phosphorylation of the insulin-receptor and AKT. Phosphorylation of GSK3 was also significantly decreased, indicating increased GSK3 activity. This evidence of reduced insulin-signaling was associated with a concomitant increase in tau phosphorylation and amyloid β protein levels. Changes in phosphorylation levels of insulin receptor, GSK3 and tau were not observed in the brain of db/db mice, a model of type-2 diabetes, after a similar duration (8 weeks) of diabetes. Treatment with insulin from onset of diabetes partially restored the phosphorylation of insulin receptor and of GSK3, partially reduced the level of phosphorylated tau in the brain and partially improved learning ability in insulin-deficient diabetic mice.
Our data indicate that mice with systemic insulin deficiency display evidence of reduced insulin-signaling pathway activity in the brain that is associated with biochemical and behavioral features of AD, and that it can be corrected by insulin treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.