Targeting Insulin-Degrading Enzyme in Insulin Clearance

Leissring, Malcolm A.; González-Casimiro, Carlos M.; Merino, Beatriz; Suire, Caitlin N.; Perdomo, Germán

doi:10.3390/ijms22052235

Open AccessReview

Targeting Insulin-Degrading Enzyme in Insulin Clearance

by

Malcolm A. Leissring

^1,*

,

Carlos M. González-Casimiro

²

,

Beatriz Merino

²

,

Caitlin N. Suire

³

and

Germán Perdomo

^2,*

¹

Institute for Memory Impairments and Neurological Disorders, University of California, Irvine (UCI MIND), Irvine, CA 92697-4545, USA

²

Instituto de Biología y Genética Molecular (University of Valladolid-CSIC), 47003 Valladolid, Spain

³

Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306-4300, USA

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2021, 22(5), 2235; https://doi.org/10.3390/ijms22052235

Submission received: 28 January 2021 / Revised: 20 February 2021 / Accepted: 21 February 2021 / Published: 24 February 2021

(This article belongs to the Special Issue Role of Insulin Clearance in Insulin Action and Metabolic Diseases)

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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.

Keywords: insulin-degrading enzyme; insulin clearance; liver; pharmacological inhibitors; insulin resistance

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MDPI and ACS Style

Leissring, M.A.; González-Casimiro, C.M.; Merino, B.; Suire, C.N.; Perdomo, G. Targeting Insulin-Degrading Enzyme in Insulin Clearance. Int. J. Mol. Sci. 2021, 22, 2235. https://doi.org/10.3390/ijms22052235

AMA Style

Leissring MA, González-Casimiro CM, Merino B, Suire CN, Perdomo G. Targeting Insulin-Degrading Enzyme in Insulin Clearance. International Journal of Molecular Sciences. 2021; 22(5):2235. https://doi.org/10.3390/ijms22052235

Chicago/Turabian Style

Leissring, Malcolm A., Carlos M. González-Casimiro, Beatriz Merino, Caitlin N. Suire, and Germán Perdomo. 2021. "Targeting Insulin-Degrading Enzyme in Insulin Clearance" International Journal of Molecular Sciences 22, no. 5: 2235. https://doi.org/10.3390/ijms22052235

APA Style

Leissring, M. A., González-Casimiro, C. M., Merino, B., Suire, C. N., & Perdomo, G. (2021). Targeting Insulin-Degrading Enzyme in Insulin Clearance. International Journal of Molecular Sciences, 22(5), 2235. https://doi.org/10.3390/ijms22052235

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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Targeting Insulin-Degrading Enzyme in Insulin Clearance

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