Targeting Insulin-Degrading Enzyme in Insulin Clearance

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Mar 6

PMID 33668109

Citations 22

Authors

Malcolm A Leissring

Carlos M Gonzalez-Casimiro

Beatriz Merino

Caitlin N Suire

German Perdomo

Affiliations

Soon will be listed here.

Abstract

Hepatic insulin clearance, a physiological process that in response to nutritional cues clears ~50-80% of circulating insulin, is emerging as an important factor in our understanding of the pathogenesis of type 2 diabetes mellitus (T2DM). Insulin-degrading enzyme (IDE) is a highly conserved Zn-metalloprotease that degrades insulin and several other intermediate-size peptides. Both, insulin clearance and IDE activity are reduced in diabetic patients, albeit the cause-effect relationship in humans remains unproven. Because historically IDE has been proposed as the main enzyme involved in insulin degradation, efforts in the development of IDE inhibitors as therapeutics in diabetic patients has attracted attention during the last decades. In this review, we retrace the path from Mirsky's seminal discovery of IDE to the present, highlighting the pros and cons of the development of IDE inhibitors as a pharmacological approach to treating diabetic patients.

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