Determinants of the IDE-Dependent Degradation of Insulin

Insulin-degrading enzyme (IDE) is an attractive target for the development of therapeutic strategies for type-2 diabetes mellitus and Alzheimer’s disease (AD). This enzyme selectively degrades small substrates including insulin and amyloid-β peptide (Aβ) that forms toxic assemblies associated with A...

Full description

Saved in:

Bibliographic Details
Main Author:	Kebede, Micheal T
Format:	Dissertation
Language:	English
Published:	ProQuest Dissertations & Theses 01-01-2019
Subjects:	Biochemistry Biophysics Chemistry
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Insulin-degrading enzyme (IDE) is an attractive target for the development of therapeutic strategies for type-2 diabetes mellitus and Alzheimer’s disease (AD). This enzyme selectively degrades small substrates including insulin and amyloid-β peptide (Aβ) that forms toxic assemblies associated with AD. With the goal of selectively modulating IDE’s proteolytic activity towards its substrates, this work examined the effects of polyphenols and model membranes on the IDE-dependent degradation of insulin. It was found that polyphenols including epigallocatechin gallate and rosmarinic acid inhibit the IDE-dependent degradation of insulin. On the other hand, resveratrol, which has been shown by Krasinski et al. to sustain the activity of IDE towards Aβ does not affect the activity of IDE towards insulin (Krasinski et al., ACS Omega, 13275-13282, 2018). Additionally, it was found that model membranes containing anionic lipids enhance the rate of insulin degradation. Membranes that contain zwitterionic lipids, on the other hand, has no effect. These findings suggest that polyphenols and lipid composition of membranes may selectively modulate IDE’s activity towards its most important substrates.
ISBN:	9781085652278 1085652270