Differential Effects of Polyphenols on Insulin Proteolysis by the Insulin-Degrading Enzyme

The insulin-degrading enzyme (IDE) possesses a strong ability to degrade insulin and A beta 42 that has been linked to the neurodegeneration in Alzheimer's disease (AD). Given this, an attractive IDE-centric strategy for the development of therapeutics for AD is to boost IDE's activity for the clearance of A beta 42 without offsetting insulin proteostasis. Recently, we showed that resveratrol enhances IDE's activity toward A beta 42. In this work, we used a combination of chromatographic and spectroscopic techniques to investigate the effects of resveratrol on IDE's activity toward insulin. For comparison, we also studied epigallocatechin-3-gallate (EGCG). Our results show that the two polyphenols affect the IDE-dependent degradation of insulin in different ways: EGCG inhibits IDE while resveratrol has no effect. These findings suggest that polyphenols provide a path for developing therapeutic strategies that can selectively target IDE substrate specificity.

Automated summary

The study found that resveratrol enhances IDE's activity toward A beta 42, while EGCG inhibits IDE's activity. These findings suggest a potential path for developing therapeutic strategies that can selectively target IDE substrate specificity.