To contribute in the understanding of IDE's role in glucose metabolism, we analyzed IDE protein level in pancreatic islets from two hyperinsulinemic mouse models, db/db and high-fat diet (HFD) mice, as well as in human islets from DM2 patients treated with oral hypoglycemic agents (OHAs) or insulin.
These results suggest that PPARgamma transcriptionally induces IDE expression which provides a novel mechanism for the use of PPARgamma agonists in both DM2 and AD therapies.
We conclude that naturally occurring, partial loss-of-function mutations in IDE sufficient to cause DM2 also impair neuronal regulation of Abeta levels, but the brain can apparently compensate for the partial deficit during the life span of the rat.
Two substrates of insulin-degrading enzyme (IDE), amyloid beta-protein (Abeta) and insulin, are critically important in the pathogenesis of Alzheimer's disease (AD) and type 2 diabetes mellitus (DM2), respectively.