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Updated: Nov 15, 2025

Assessing Insulin Clearance in Mice via In Situ Liver Perfusion
Published on: December 13, 2024
Targeting Insulin-Degrading Enzyme in Insulin Clearance
Malcolm A Leissring1, Carlos M González-Casimiro2, Beatriz Merino2
1Institute for Memory Impairments and Neurological Disorders, University of California, Irvine (UCI MIND), Irvine, CA 92697-4545, USA.
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 Zn2+-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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