Differential Effects Of Polyphenols On Insulin Proteolysis By The Insulin-Degrading Enzyme

ANTIOXIDANTS(2021)

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摘要
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.
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关键词
polyphenols, resveratrol, epigallocatechin-3-gallate, insulin-degrading enzyme
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