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

Qiuchen Zheng; Micheal T. Kebede; Bethany Lee; Claire A. Krasinski; Saadman Islam; Liliana A. Wurfl; Merc M. Kemeh; Valerie A. Ivancic; Charles E. Jakobsche; Donald E. Spratt; Noel D. Lazo

doi:10.3390/antiox10091342

Antioxidants (Aug 2021)

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

Qiuchen Zheng,
Micheal T. Kebede,
Bethany Lee,
Claire A. Krasinski,
Saadman Islam,
Liliana A. Wurfl,
Merc M. Kemeh,
Valerie A. Ivancic,
Charles E. Jakobsche,
Donald E. Spratt,
Noel D. Lazo

Affiliations

Qiuchen Zheng: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA
Micheal T. Kebede: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA
Bethany Lee: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA
Claire A. Krasinski: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA
Saadman Islam: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA
Liliana A. Wurfl: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA
Merc M. Kemeh: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA
Valerie A. Ivancic: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA
Charles E. Jakobsche: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA
Donald E. Spratt: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA
Noel D. Lazo: Gustaf H. Carlson School of Chemistry and Biochemistry, Clark University, Worcester, MA 01610, USA

DOI: https://doi.org/10.3390/antiox10091342
Journal volume & issue: Vol. 10, no. 9
p. 1342

Abstract

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The insulin-degrading enzyme (IDE) possesses a strong ability to degrade insulin and Aβ42 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 Aβ42 without offsetting insulin proteostasis. Recently, we showed that resveratrol enhances IDE’s activity toward Aβ42. 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.

Published in Antioxidants

ISSN: 2076-3921 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.mdpi.com/journal/antioxidants

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